Antineoplastic agents t

• T1e28z car-expressing autologous cd4-positive t lymphocytes - Autologous CD4 positive T-lymphocytes engineered to express the chimeric antigen receptor (CAR) T1E28z containing the ErbB ligand, T1E, fused to the hinge region, transmembrane domain and endodomain of CD28 and the CD3zeta endodomain, with potential immunomodulating and antineoplastic activities. T1E, a chimeric polypeptide containing the N-terminus of human transforming growth factor (TGF)-alpha fused to the C-terminus of epidermal growth factor (EGF), binds to ErbB1 homodimers and heterodimers as well as ErbB2/3 heterodimers, but not to ErbB2 or erbB3 alone. Upon intratumoral administration, the promiscuous ErbB ligand T1E of the T1E28z CAR-expressing autologous CD4-positive T lymphocytes binds to the specific ErbB homo- and heterodimers on tumor cells. This induces selective toxicity in ErbB-expressing tumor cells resulting in tumor cell lysis. ErbB1, ErbB2 and ErbB3, members of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, are frequently overexpressed in solid tumors and play key roles in tumor cell proliferation and tumor angiogenesis.

• T4n5 liposomal lotion - A topical lotion that contains the enzyme T4-bacteriophage endonuclease V encapsulated within liposomes. With topical liposomal delivery, the DNA repair enzyme T4-bacteriophage endonuclease V is transported into skin cells, where the enzyme enters cell nuclei and binds to and incises pyrimidine dimers, thereby catalyzing the first reaction step of the cellular excision repair pathway for removing DNA replication-inhibiting pyrimidine dimers produced within duplex DNA through exposure to ultraviolet (UV) irradiation. In vitro and in vivo studies indicate that T4N5 liposomes increases repair of DNA damage caused by UV irradiation. (NCI05)

• T900607 - A pentafluorophenylsulfonamide compound with potential antineoplastic activity. T900607 inhibits tubulin polymerization by binding irreversibly to colchicine binding sites, resulting in cell cycle arrest and apoptosis.

• Tabalumab - A human IgG4 monoclonal antibody against B-cell activating factor (BAFF), with potential immunomodulating and antineoplastic activities. Tabalumab binds to and inhibits the activity of both soluble and cell surface-bound BAFF. This may reduce the activity, proliferation and survival of B-cells. A dysregulated expression of BAFF, a member of the tumor necrosis factor (TNF) family of proteins, is often seen in certain autoimmune diseases and certain cancers, and may promote B lymphocyte activation, proliferation and survival.

• Tabelecleucel - Allogeneic cytotoxic T-lymphocytes (CTLs) selective for the tumor-associated antigens (TAAs) expressed by the Epstein-Barr virus (EBV), with potential immunostimulating and antineoplastic activities. Upon administration, and after hematopoietic cell transplants (HCT) or solid organ transplants (SOT), or during certain other immunocompromised states, tabelecleucel targets and binds to EBV-associated antigens expressed on EBV-infected cells. This results in lysis of EBV-infected cells and prevents growth of EBV-associated cancer cells. EBV is associated with a variety of cancers and post-transplant lymphoproliferative disorders (EBV+ PTLD).

• Tacedinaline - An orally bioavailable substituted benzamide derivative with potential antineoplastic activity. Tacedinaline inhibits histone deacetylation, which may result in histone hyperacetylation, followed by the induction of differentiation, the inhibition of cell proliferation, and apoptosis in susceptible tumor cell populations.

• Taek-vac-herby vaccine - A cancer vaccine targeting the tumor-associated antigen (TAA) HER-2/neu (ErbB-2), with potential immunomodulating and antineoplastic activities. Upon administration, TAEK-VAC-HerBy vaccine may induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells expressing the HER-2/neu antigen, which may result in the inhibition of proliferation in Her-2/neu-expressing tumor cells. Her-2/neu, a member of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, is overexpressed in various tumor cell types.

• Tafasitamab - An Fc engineered, humanized anti-CD19 monoclonal antibody directed against the B-cell-specific membrane protein CD19 with potential immunostimulating and antineoplastic activities.Tafasitamab targets and binds to CD19, thereby depleting and eliminating CD19-expressing B-cells. The modified Fc region of XmAb5574 increases binding affinity to Fc-gamma receptors of effector cells and thereby enhances antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). CD19 is widely expressed during B-cell development, from pro-B-cell to early plasma cell stages.

• Tag-7 gene-modified vaccine - A cell-based vaccine composed of autologus inactivated tumor cells that have been genetically modified with the gene encoding for the innate immunity protein peptidoglycan recognition protein 1 (Tag7; PGRP-S; PGLYRP1; TAG-7), with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration of Tag-7 gene-modified vaccine (GMV), the Tag-7 transfected tumor cells express Tag-7 which is presented to the immune system and activates the innate immune system. This may activate the immune system to exert a T-lymphocyte-mediated immune response against Tag-7-expressing tumor cells.

• Tagraxofusp-erzs - A recombinant protein consisting of human interleukin 3 (IL3) fused to the first 388 amino acids of diphtheria toxin [DT(388)] (DT388IL3) with potential antineoplastic activity. Upon intravenous administration of tagraxofusp-erzs, the IL3 moiety binds to IL3 receptors on cells expressing the receptor. Subsequently, the DT(388) toxin moiety, which contains both translocation and catalytic domains, is transported across the cell membrane via endocytosis. Within the cytosol, the catalytic domain of the toxin both catalyzes the ADP-ribosylation of, and inactivates, translation elongation factor 2 (EF-2), which results in the inhibition of translation during protein synthesis. IL3 may be overexpressed by a variety of cancers, including blastic plasmacytoid dendritic cell neoplasm and acute myeloid leukemia (AML).

• Talabostat - A small molecule with antineoplastic and hematopoiesis- stimulating activities. By cleaving N-terminal Xaa-Pro or Xaa-Ala residues, talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell dependent activity. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis. Dipeptidyl peptidases are involved in the activation of polypeptide hormones and chemokines.

• Talabostat mesylate - The mesylate salt of an orally active small molecule with antineoplastic and hematopoiesis- stimulating activities. By cleaving N-terminal Xaa-Pro or Xaa-Ala residues, talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell dependent activity. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis. Dipeptidyl peptidases are involved in the activation of polypeptide hormones and chemokines.

• Talacotuzumab - A humanized IgG1 monoclonal antibody against CD123 (Interleukin-3 receptor alpha chain or IL3RA) with potential antineoplastic activity. Upon intravenous administration, talacotuzumab binds to and neutralizes CD123. This may inhibit IL-3-dependent signaling and may inhibit proliferation and differentiation in CD123-positive tumor cells. CSL362 contains an engineered Fc region which increases its binding affinity to Fc-gamma receptors on the surface of natural killer (NK) cells thereby initiating antibody-dependent cellular cytotoxicity (ADCC). CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness.

• Talactoferrin alfa - An orally bioavailable recombinant human lactoferrin produced in the fungus Aspergillus niger with potential antineoplastic and immunomodulating activities. Upon oral administration, talactoferrin is transported into small intestinal Peyer's patches of the gut-associated lymphoreticular tissues (GALT), where it recruits circulating immature dendritic cells (DCs) bearing tumor antigens and induces their maturation. In the GALT, DC maturation in the presence of tumor antigens and lymphoid effector cells may induce systemic innate and adaptive immune responses mediated by anti-tumor natural killer (NK) cells, cytotoxic T lymphocytes, and natural killer T (NKT) cells; activation of tumor-draining lymph nodes, cellular infiltration of distant tumors, and tumor-cell death may follow. Raising the initial immune response in the GALT, distant from the primary tumor, may counter local tumor-mediated immunosuppression.

• Taladegib - An orally bioavailable small molecule antagonist of the Hedgehog (Hh)-ligand cell surface receptor smoothened (Smo) with potential antineoplastic activity. Taladegib inhibits signaling that is mediated by the Hh pathway protein Smo, which may result in a suppression of the Hh signaling pathway and may lead to the inhibition of the proliferation of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers.

• Talampanel - A synthetic derivative of dioxolo-benzodiazepine with anti-seizure activity. Talampanel antagonizes the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subtype of glutamate excitatory amino acid receptors and may inhibit the growth of gliomas by interfering with neurotransmitters involved in brain tumor growth. This agent may also protect against traumatic brain injury.

• Talaporfin sodium - An agent consisting of chlorin e6, derived from chlorophyll, and L-aspartic acid with photosensitizing activity. After intratumoral activation by light emitting diodes, taporfin sodium forms an extended high energy conformational state that generates singlet oxygen, resulting in free radical-mediated cell death.

• Talazoparib - An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity. Talazoparib selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.

• Taletrectinib - An orally available inhibitor of the receptor tyrosine kinases C-ros oncogene 1 (ROS1) and the neurotrophic tyrosine receptor kinase (NTRK) types 1, 2 and 3, with potential antineoplastic activity. Upon oral administration, taletrectinib binds to and inhibits ROS1 and the NTRK family members. This inhibition leads to a disruption of ROS1- and NTRK-mediated signaling and eventually inhibits the growth of tumor cells that are overexpressing ROS1 and/or NTRKs. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells. NTRK mutations or rearrangements play a key role in cancer progression.

• Talimogene laherparepvec - An ICP34.5, ICP47-deleted, oncolytic herpes simplex type-1 virus (HSV-1) based on the JS1 strain, and encoding the immunostimulating factor human cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) with potential immunostimulating and antineoplastic activities. Upon intratumoral injection, talimogene laherparepvec selectively infects and replicates in tumor cells, thereby inducing tumor cell lysis. In addition, GM-CSF attracts dendritic cells (DCs) and may stimulate a cytotoxic T cell response against tumor cells, which results in immune-mediated tumor cell death. Deletion of the gene encoding for ICP34.5 provides tumor selectivity and prevents replication in healthy cells. As ICP47 blocks antigen presentation in HSV-infected cells, deletion of this gene may induce a more potent antitumor immune response in the tumor cells. Additionally, deletion of ICP47 causes increased expression of the HSV US11 gene and allows US11 to be expressed as an immediate early and not a late gene. This further enhances the degree of viral replication and oncolysis of tumor cells.

• Tallimustine - A benzoyl mustard derivative of the antiviral agent distamycin A with potential antineoplastic activity. Tallimustine selectively binds to A-T rich regions in the minor groove of DNA and alkylates at the N3 position of adenine in a highly sequence-specific manner. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. Moreover, unlike other clinical nitrogen mustards, tallimustine does not carry out guanine-N7 alkylation in the major groove of DNA, which may lead to a high selectivity of action.

• Talmapimod - An orally bioavailable, small-molecule, p38 mitogen-activated protein kinase (MAPK) inhibitor with potential immunomodulating, anti-inflammatory, and antineoplastic activities. Talmapimod specifically binds to and inhibits the phosphorylation of p38 MAPK, which may result in the induction of tumor cell apoptosis, the inhibition of tumor cell proliferation, and the inhibition of tumor angiogenesis. This agent may also enhance proteasome inhibitor-induced apoptosis. p38 MAPK is a serine/threonine protein kinase involved in a MAPK signaling cascade that controls cellular responses to various environmental stresses, cytokines, and endotoxins.

• Talotrexin - An antimetabolite analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.

• Talotrexin ammonium - An ammonium salt of tallotrexin, an analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.

• Taltobulin - An analogue of the naturally occurring tripeptide hemiasterlin, with potential antimitotic and antineoplastic activities. Taltobulin binds tubulin in a similar manner as colchicine and inhibits tubulin polymerization. This results in the disruption of the cytoskeleton, ultimately leading to cell cycle arrest in G2/M phase, blockage of cell division and apoptosis.

• Tam/c-met inhibitor rxdx-106 - An orally available and selective inhibitor of the receptor tyrosine kinase (RTK) activity of both hepatocyte growth factor receptor (c-Met; HGFR) and receptors in the TYRO3, AXL, and MER (TAM) family, with potential immunomodulating and antineoplastic activities. Upon oral administration of TAM/c-Met inhibitor RXDX-106, this agent selectively targets and binds to TYRO3, AXL, MER and c-Met, and prevents their RTK activity. This blocks TYRO3/AXL/MER/c-Met-mediated signal transduction pathways, and inhibits the proliferation and migration of TYRO3-, AXL-, MER- and c-Met-overexpressing tumor cells. Inhibition of the TAM family in the tumor microenvironment (TME) activates the immune system in the TME, reverses TAM mediated immunosuppression and enhances the anti-tumor immune response, which lead to immune-mediated tumor cell killing. TYRO3, AXL and MER, members of the TAM family of RTKs, are overexpressed in many tumor cell types. TAMs play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with drug resistance and poor prognosis. c-Met, also overexpressed in many tumor cell types, plays a critical role in tumor formation, proliferation, invasion and metastasis, and contributes to tumor resistance. In the TME, TAM expression on immune cells contributes to tumor cell evasion of immune surveillance and to the negative regulation of immune responses.

• Tamibarotene - An orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity. As a specific retinoic acid receptor (RAR) alpha/beta agonist, tamibarotene is approximately ten times more potent than ATRA in inducing cell differentiation and apoptosis in HL-60 (human promyelocytic leukemia) cell lines in vitro. Due to a lower affinity for cellular retinoic acid binding protein (CRABP), tamibarotene may show sustained plasma levels compared to ATRA. In addition, this agent may exhibit a lower toxicity profile than ATRA, in part, due to the lack of affinity for the RAR-gamma receptor, the major retinoic acid receptor in the dermal epithelium.

• Taminadenant - An orally bioavailable adenosine A2A receptor (A2AR) antagonist, with potential antineoplastic activity. Upon administration, A2AR antagonist PBF-509 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This abrogates the adenosine/A2AR-mediated inhibition of T-lymphocytes and activates a T-cell-mediated immune response against tumor cells, thereby reducing proliferation of susceptible tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often produced in excess by cancer cells.

• Tamoxifen - An antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth.

• Tamoxifen citrate - The citrate salt of an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth. Tamoxifen also down-regulates protein kinase C (PKC) expression in a dose-dependant manner, inhibiting signal transduction and producing an antiproliferative effect in tumors such as malignant glioma and other cancers that overexpress PKC.

• Tamrintamab pamozirine - An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against a tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration of tamrintamab pamozirine, the monoclonal antibody moiety of SC-003 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.

• Tandutinib - A piperazinyl quinazoline receptor tyrosine kinase inhibitor with antineoplastic activity. Tandutinib inhibits the autophosphorylation of FLT3 (FMS-Like Tyrosine kinase-3), c-KIT and PDGF (platelet-derived growth factor) receptor tyrosine kinases, thereby inhibiting cellular proliferation and inducing apoptosis.

• Tanespimycin - A benzoquinone antineoplastic antibiotic derived from the antineoplastic antibiotic geldanamycin. Tanespimycin binds to and inhibits the cytosolic chaperone functions of heat shock protein 90 (HSP90). HSP90 maintains the stability and functional shape of many oncogenic signaling proteins; the inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins that may be overexpressed by tumor cells.

• Tankyrase inhibitor stp1002 - An orally bioavailable inhibitor of the poly (ADP-ribose) polymerase (PARP) enzyme tankyrase, with potential antineoplastic activity. Upon administration, tankyrase inhibitor STP1002 selectively binds to and inhibits the activity of tankyrase. This may block the tankyrase-mediated poly(ADP-ribosyl)ation of multiple target proteins including various tumor suppressors. This may include the blockage of the poly(ADP-ribosyl)ation and destabilization of AXIN, a negative regulator of beta-catenin, and prevents Wnt/beta-catenin signaling. This may inhibit the activation of transcription of a wide range of target genes of Wnt/beta-catenin signaling, thereby preventing gene expression of many Wnt-related, pro-survival proteins and suppressing tumor cell growth. Tankyrase, a member of the PARP family, plays an important role in the regulation of the Wnt/beta-catenin signaling pathway, tumor suppressors, as well as telomere maintenance and mitosis regulation.

• Tanomastat - A biphenyl matrix metalloproteinase (MMP) inhibitor (MMPI) with potential antineoplastic activity. Tanomastat inhibits MMP-2, MMP-3, and MMP-9, inhibiting extracellular matrix degradation and potentially inhibiting angiogenesis, tumor growth and invasion, and metastasis. MMPs consist of at least 18 zinc-containing endo-proteinases that are capable of degrading collagen and proteoglycan.

• Tapotoclax - An inhibitor of induced myeloid leukemia cell differentiation protein MCL-1 (myeloid cell leukemia-1), with potential pro-apoptotic and antineoplastic activities. Upon administration, tapotoclax binds to and inhibits the activity of MCL-1. This disrupts the formation of MCL-1/Bcl-2-like protein 11 (BCL2L11; BIM) complexes and induces apoptosis in tumor cells. MCL-1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival.

• Tarenflurbil - An orally active synthetic enantiomer of flurbiprofen. Tarenflurbil activates c-Jun N terminal kinase, increases AP-1 binding to DNA, and downregulates cyclin D1 expression, resulting in arrest of tumor cells in the G1 phase of the cell cycle and apoptosis. This agent also affects the expression of nuclear factor kappa B, a rapid response transcription factor that stimulates the immune response to tumor cells. R-flurbiprofen does not inhibit the enzyme cyclo-oxygenase.

• Tarextumab - A monoclonal antibody directed against the Notch receptor with potential antineoplastic activity. Tarextumab binds to Notch on the cell surface, thereby inhibiting Notch-mediated signaling and gene transcription, which may impede tumor angiogenesis. Notch receptors are important for cell-cell communication, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Dysregulated Notch signaling is implicated in many diseases including T-ALL (T-cell acute lymphoblastic leukemia), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), MS (Multiple Sclerosis), and many other disease states.

• Targeted therapy agent - Any agent that specifically targets or interferes with the synthesis or function of a molecule that is expressed specifically in or on cells of the tumor and/or the tumor microenvironment (TME), such as immune cells or surrounding blood vessels. The targeted molecule is usually overexpressed or mutated in tumor cells but minimally or not expressed by normal, healthy cells; additionally, expression is typically associated with tumor cell proliferation, progression and/or survival. By blocking the function or expression of the tumo-associated target, the targeted therapy agent may exert potential antineoplastic and/or immunomodulatory activities.

• Tariquidar - An anthranilamide derivative with multidrug resistance properties. Tariquidar non-competitively binds to the p-glycoprotein transporter, thereby inhibiting transmembrane transport of anticancer drugs. Inhibition of transmembrane transport may result in increased intracellular concentrations of an anticancer drug, thereby augmenting its cytotoxicity.

• Tarp 27-35 peptide vaccine - A peptide-based cancer vaccine, containing amino acid residues 27 through 35 of T cell receptor gamma alternate reading frame protein (TARP), with potential immunostimulatory and antineoplastic activities. Upon administration, TARP 27-35 peptide vaccine may stimulate a host cytotoxic T-cell (CTL) response against TARP-expressing tumor cells, resulting in tumor cell cytotoxicity. The nuclear protein TARP is commonly expressed on prostate and breast cancer cells and is highly immunogenic.

• Tarp 29-37-9v peptide vaccine - A peptide-based cancer vaccine, consisting of amino acid residues 29 through 37 of T cell receptor gamma alternate reading frame protein (TARP) with a leucine-to-valine substitution at position 9, with potential immunostimulatory and antineoplastic activities. Upon administration, TARP 29-37-9V peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against TARP-expressing tumor cells, which may result in decreased tumor cell proliferation. The leucine-to-valine substitution at position 9 of this peptide improves its immunogenicity. The nuclear protein TARP is commonly expressed on prostate and breast cancer cells and is highly immunogenic.

• Tasadenoturev - An adenovirus serotype 5 strain, selectively replication competent in cells defective in the Rb/p16 tumor suppressor pathway, with potential oncolytic activity. Tasadenoturev contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of tumor cells, which are often deficient for Coxsackie and adenovirus receptors (CARs). Selectively replication competent in cells that are defective in retinoblastoma gene (Rb) or cyclin-dependent kinase inhibitor-2A (p16), active replication of oncolytic adenovirus Ad5-Delta 24RGD in tumor cells may induce oncolysis or cell lysis. As integral components of the late G1 restriction point, the Rb gene product and p16 are negative regulators of the cell cycle; ovarian cancer cells and non-small cell lung cancer cells may be defective in the Rb/p16 pathway.

• Tasadenoturev-infected allogeneic bone marrow-derived mesenchymal stem cells - A preparation of bone marrow-derived allogeneic mesenchymal stem cells (MSCs) infected with tasadenoturev (Ad5-DNX-2401), an adenovirus serotype 5 strain that is selectively replication competent in cells defective in the Rb/p16 tumor suppressor pathway, with potential antineoplastic activity. Upon infusion of the tasadenoturev-infected bone marrow-derived MSCs, these cells target and deliver the adenovirus to tumor cells. The oncolytic virus then selectively transfects and replicates in the tumor cells, eventually leading to tumor cell lysis and the release of virus particles and various tumor associated antigens (TAAs). This may induce a systemic immune response against tumor cells expressing these TAAs and further infection and killing of nearby tumor cells by the released viral particles. Ad5-DNX-2401 contains an integrin binding RGD-4C motif, allowing Coxsackievirus and adenovirus receptor-independent infection of tumor cells, which are often deficient for Coxsackievirus and adenovirus receptors (CARs). As integral components of the late G1 restriction point, the Rb gene product and p16 are negative regulators of the cell cycle and are often defective in certain cancer types.

• Taselisib - An orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) alpha isoform (PIK3CA), with potential antineoplastic activity. Taselisib selectively inhibits PIK3CA and its mutant forms in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting class I PI3K alpha, this agent may be more efficacious and less toxic than pan PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and causes increased tumor cell growth, survival, and resistance to both chemotherapy and radiotherapy. PIK3CA, which encodes the p110-alpha catalytic subunit of the class I PI3K, is mutated in a variety of cancer cell types and plays a key role in cancer cell growth and invasion.

• Tasidotin - A third generation, synthetic, water-soluble, pentapeptide analog of the marine depsipeptide dolastatin 15, with potential antimitotic and antineoplastic activities. Tasidotin and its metabolite, tasidotin C-carboxylate, suppress the dynamic instability behavior of the microtubules through a reduction of the shortening rate (disassembly); reduction of the switching frequency from growth to shortening; and by reducing microtubules growth time. This may eventually result in a reduction of cell growth.

• Tasisulam - An acyl-sulfonamide with potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS). In combination with an angiogenesis inhibitor, this agent may exhibit synergistic antiangiogenic activity.

• Tasisulam sodium - The sodium salt of an acyl-sulfonamide with potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS). In combination with an angiogenesis inhibitor, this agent may exhibit synergistic antiangiogenic activity.

• Tasquinimod - A quinoline-3-carboxamide linomide analogue with antiangiogenic and potential antineoplastic activities. Tasquinimod has been shown to decrease blood vessel density but the exact mechanism of action is not known. This agent has also been shown to augment the antineoplastic effects of docetaxel and androgen ablation in a murine model of prostate cancer involving human prostate cancer xenografts.

• Taurolidine - A synthetic broad-spectrum antibiotic with antibacterial, anticoagulant and potential antiangiogenic activities. Taurolidine, derived from the amino acid taurine, binds to and neutralizes bacterial exotoxins and endotoxins, or lipopolysaccharides (LPS). Taurolidine binding to LPS prevents bacterial adherence to host epithelial cells, thereby prevents bacterial invasion of uninfected host cells. Although the mechanism underlying its antineoplastic activity has not been fully elucidated, it may be related to this agent's anti-adherence property. In addition, taurolidine also promotes apoptosis by inducing various apoptotic factors and suppresses the production of vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis.

• Tauromustine - A water-soluble taurine-based nitrosourea with potential antineoplastic activity. Tauromustine alkylates DNA and causes DNA cross links independent of cell cycle, thereby resulting in disruption of DNA function and induction of apoptosis.

• Taurultam - A reversible metabolite of taurolidine and an amino acid taurine derivative, with antibacterial and antineoplastic activity. Taurultam, like its congener taurolidine, inhibits proliferation of microvascular endothelial cells, although to a lesser extent, by selectively inhibiting the adhesion of endothelial cells to laminin but not to collagen I and fibronectin.

• Taurultam analogue gp-2250 - An oxathiazine-based structural analogue of taurultam (TRLT), which is the main derivative of the anti-infective agent taurolidine (TRD), with potential antineoplastic activity. Upon administration, GP-2250 selectively induces reactive oxygen species (ROS)-mediated apoptosis in and inhibits proliferation of susceptible tumor cells.

• Tavokinogene telseplasmid - A DNA plasmid that encodes genes for both the p35 and p40 subunits of the heterodimeric human interleukin 12 (hIL-12) protein that are separated by an internal ribosome entry site (IRES) and under the control of a single cytomegalovirus (CMV) promoter, with potential immunomodulatory and antineoplastic activities. Upon administration via intratumoral injection and electroporation, the plasmid is introduced into human cells resulting in expression and highly-localized secretion of a functional IL-12 p70 protein into the tumor microenvironment (TME). IL-12 is a pro-inflammatory cytokine that plays a significant role in priming and maintaining T-helper (Th) cells, activating natural killer (NK) cells, and regulating the reactivation and survival of memory T-cells (Tm). Increased levels of IL-12 in the TME may augment host immune response against tumor cells by inhibiting regulatory T-cells (Tregs), T-helper 2 (Th2) responses, and myeloid-derived suppressor cells (MDSCs).

• Tavolimab - An agonistic, humanized monoclonal antibody against receptor OX40 (CD134), with potential immunostimulatory activity. Upon administration, tavolimab selectively binds to and activates the OX40 receptor. OX40 receptor activation induces proliferation of memory and effector T-lymphocytes. In the presence of tumor-associated antigens (TAAs), this agent may promote an immune response against TAAs-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor family, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.

• Taxane analogue tpi 287 - A synthetic, third generation taxane with potential antineoplastic activity. TPI 287 binds to tubulin and stabilizes microtubules, resulting in inhibition of microtubule assembly/disassembly dynamics, cell cycle arrest at the G2/M phase, and apoptosis.

• Taxol analogue sid 530 - An intravenous formulation containing docetaxel, a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree, Taxus baccata, with potential antineoplastic activity. Taxol analogue SID 530 binds to and stabilizes tubulin, inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death.

• Tazarotene - A synthetic, topical retinoid. Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. In psoriasis, tazarotene normalizes abnormal keratinocyte differentiation and reduces their hyperproliferation.

• Tazemetostat - An orally available, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2, with potential antineoplastic activity. Upon oral administration, tazemetostat selectively inhibits the activity of both wild-type and mutated forms of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2 mutated cancer cells. EZH2, which belongs to the class of histone methyltransferases (HMTs), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation.

• Tbc-cea-contaminated w/ bvdv - A cancer vaccine consisting of a recombinant vector encoding the tumor-associated carcinoembryonic antigen (CEA) that is contaminated with bovine viral diarrhea virus (BVDV). The carcinoembryonic antigen (CEA) is a prevalent tumor marker expressed by a number of different cancers such as colorectal, breast, lung and ovarian carcinomas; vaccination with vaccinia virus genetically engineered to express CEA may generate antitumoral T-cell responses. BVDV is an RNA pestivirus that may contaminate vaccines due to its presence in fetal calf serum used as a growth supplement in the tissue culture of mammalian cells used in vaccine production.

• Tcr-specific, alpha fetoprotein-enhanced autologous t lymphocytes - A preparation of human autologous T-lymphocytes transduced with a viral vector encoding for a T-cell receptor (TCR) specific for human alpha-fetoprotein (AFP), with potential antineoplastic activity. Following administration, the TCR-specific, alpha fetoprotein-enhanced autologous T-lymphocytes recognize and bind to AFP antigen-positive cells, which results in lysis and killing of AFP-positive cancer cells. AFP is overexpressed in a variety of cancers.

• Tebentafusp - A fusion protein containing a modified form of human T-cell receptor (TCR) specific for the gp100 antigen and fused to an anti-CD3 single-chain antibody fragment, with potential antineoplastic activity. Upon direct intratumoral administration of tebentafusp into the melanoma lesion, the TCR moiety of this agent targets and binds to the tumor associated antigen (TAA) gp100 presented on the melanoma tumor cell; the anti-CD3 fragment moiety binds to CD3- expressing T lymphocytes, thereby selectively cross-linking tumor cells and T-lymphocytes. This may lead to the recruitment of cytotoxic T lymphocytes (CTL) to the T lymphocyte/tumor cell aggregates and result in CTL-mediated death of gp100-expressing melanoma cancer cells.

• Teclistamab - A bispecific humanized monoclonal antibody against human CD3, a T-cell surface antigen, and human B-cell maturation antigen (BCMA; TNFRSF17), a tumor-associated antigen (TAA) expressed on plasma cells, with potential antineoplastic activity. Upon administration, teclistamab binds to both CD3 on T-cells and BCMA expressed on malignant plasma cells. This results in the cross-linking of T-cells and tumor cells, and induces a potent cytotoxic T-lymphocyte (CTL) response against BCMA-expressing plasma cells. BCMA, a member of the tumor necrosis factor receptor superfamily that is specifically overexpressed on malignant plasma cells, plays a key role in promoting plasma cell survival.

• Tecogalan sodium - A sulfated polysaccharide isolated from various Arthrobacter bacterial species. Possessing potential antiangiogenic and antineoplastic properties, tecogalan binds to basic fibroblast growth factor (bFGF), thereby preventing bFGF from binding to its receptors. Disruption of this receptor binding results in the inhibition of bFGF-stimulated endothelial cell growth, proliferation, and migration.

• Tefinostat - A hydroxamic acid-derived histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. Tefinostat inhibits HDAC leading to an accumulation of highly acetylated histones, which may result in chromatin remodeling, inhibition of tumor oncogene transcription, inhibition of tumor cell division, and the induction of tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins; this agent may specifically target HDACs in cells of the monocyte-macrophage lineage.

• Tegafur - A congener of the antimetabolite fluorouracil with antineoplastic activity. Tegafur is a prodrug that is gradually converted to fluorouracil in the liver by the cytochrome P-450 enzyme. Subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) by both tumor cells and normal cells. FdUMP inhibits DNA synthesis and cell division by inhibiting thymidylate synthase and reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.

• Tegafur-gimeracil-oteracil potassium - An orally bioavailable fluoropyrimidine antagonist composed of tegafur combined with two modulators of 5-fluorouracil (5-FU) activity, gimeracil and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug of 5-fluorouracil, an antimetabolite that inhibits thymidylate synthase, DNA synthesis and cell division, and competes with uridine triphosphate, thus inhibiting RNA and protein synthesis. Gimeracil is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Potassium oxonate preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyl-transferase (OPRT), thereby decreasing activation of 5-FU in the gut and activated 5-FU-related gastrointestinal toxicity.

• Tegafur-gimeracil-oteracil potassium-leucovorin calcium oral formulation - An orally bioavailable granular formulation composed of the fluoropyrimidine antagonist tegafur combined with two modulators of 5-fluorouracil (5-FU) activity, gimeracil and oteracil potassium, and the folic acid derivative leucovorin calcium, with potential antineoplastic activity. Tegafur is a prodrug of 5-fluorouracil (5-FU), an antimetabolite that is further metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits thymidylate synthase, DNA synthesis and cell division; FUTP competes with uridine triphosphate (UTP), thus inhibiting RNA and protein synthesis. Gimeracil is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Oteracil potassium preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyl-transferase (OPRT), which converts tegafur to 5-FU. This decreases the amount of 5-FU in the gut and prevents activated 5-FU-related gastrointestinal (GI) toxicity. Leucovorin calcium, an active metabolite of folic acid, counteracts the toxic effects of 5-FU, thereby 'rescuing' the patient while permitting the antitumor activity of 5-FU.

• Tegafur-uracil - A formulated therapeutic oral agent consisting of a combination of the 5-fluorouracil (5-FU) congener prodrug tegafur (tetrahydrofuranyl-5-fluorouracil) and uracil (1:4). The high concentration of uracil reversibly inhibits the uracil-reducing enzyme dihydropyrimidine dehydrogenase (DPD), thereby inhibiting first-pass DPD-mediated hepatic metabolism of the uracil analogue 5-FU and permitting administration of 5-FU as the orally bioavailable prodrug tegafur. Tegafur is bioactivated to 5-FU by liver microsomal cytochrome P450 enzymes. 5-FU is subsequently converted into its active metabolites 5-fluoro-deoxyuridine-monophosphate (FdUMP) and 5-fluorouridine-triphosphate (FUTP) intracellularly; these metabolites inhibit the enzyme thymidylate synthase and intercalate into RNA, resulting in decreased thymidine synthesis, reduced DNA synthesis, disrupted RNA function, and tumor cell cytotoxicity.

• Tegavivint - A small molecule inhibitor of the Wnt/beta-catenin pathway with potential antineoplastic activity. Upon intravenous administration, tegavivint binds to transducin beta-like protein 1 (TBL1) and disrupts the binding of beta-catenin to TBL1. This promotes beta-catenin degradation, attenuates nuclear and cytoplasmic levels of beta-catenin, and reduces transcriptional activity of transcription factor 4 (TCF4) and expression of its target genes, cyclin D1, c-Myc and survivin. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation. Beta-catenin is frequently mutated in various tumors.

• Teglarinad - A water-soluble prodrug of a pyridyl cyanoguanidine compound and an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with potential antineoplastic activity. Teglarinad is rapidly converted in the bloodstream into an active compound through hydrolytic cleavage of the carbonate ester bond. The activated form inhibits NAMPT, thereby inhibiting nicotinamide adenine dinucleotide (NAD+) biosynthesis and induces a rapid decline in intracellular NAD+ followed by ATP reduction. As NAD+ is essential for tumor cell growth, inhibition of NAMPT induces tumor cell death. NAMPT is an essential enzyme in the synthesis of NAD+ and is upregulated in some cancers.

• Teglarinad chloride - A water-soluble prodrug of a cyanoguanidine compound with potential antineoplastic activity. In vivo, teglarinad chloride is rapidly converted into active drug through hydrolytic cleavage of a carbonate ester bond. Although the exact mechanism of action has yet to be fully elucidated, the active drug appears to antagonize nuclear factor-kappa B (NF-kB) transcription, resulting in the induction of tumor cell apoptosis.

• Telaglenastat - An orally bioavailable inhibitor of glutaminase, with potential antineoplastic activity. Upon oral administration, CB-839 selectively and irreversibly inhibits glutaminase, a mitochondrial enzyme that is essential for the conversion of the amino acid glutamine into glutamate. By blocking glutamine utilization, proliferation in rapidly growing cells is impaired. Glutamine-dependent tumors rely on the conversion of exogenous glutamine into glutamate and glutamate metabolites to both provide energy and generate building blocks for the production of macromolecules, which are needed for cellular growth and survival.

• Telaglenastat hydrochloride - The hydrochloride salt form of CB-839, an orally bioavailable inhibitor of glutaminase, with potential antineoplastic and immunostimulating activities. Upon oral administration, CB-839 selectively and reversibly binds to and inhibits human glutaminase, an enzyme that is essential for the conversion of the amino acid glutamine into glutamate. Blocking glutamine metabolism inhibits proliferation in rapidly growing tumor cells and leads to an induction of cell death. Unlike normal healthy cells, glutamine-dependent tumors heavily rely on the intracellular conversion of exogenous glutamine into glutamate and glutamate metabolites to both provide energy and generate building blocks for the production of macromolecules, which are needed for cellular growth and survival. In addition, CB-839 causes accumulation of glutamine in tumor cells and increases glutamine concentration in the tumor microenvironment (TME) upon cell death. As glutamine is essential for T-cell generation, CB-839 may also enhance T-cell proliferation and activation in the TME, which may lead to further killing of tumor cells.

• Telapristone - An orally available 21-substituted-19-nor-progestin and selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Upon oral administration, telapristone competitively binds to the progesterone receptor (PR) in progesterone-responsive tissue and inhibits PR-mediated gene expression. This interferes with progesterone activity in the reproductive system. As a result, this agent may suppress ovulation and inhibit proliferation of endometrial tissue. Also, this agent may prevent cell growth and induce apoptosis in estrogen receptor (ER) and PR-positive breast cancer cells through a reduction in progesterone levels, ER downregulation and a suppression of the expression of cyclin-dependent kinases (CDK) 2 and 4, ultimately leading to G1/S cell cycle arrest. Unlike some other SPRMs, this agent does not exert any estrogenic, androgenic, anti-estrogenic, and anti-androgenic activities.

• Telapristone acetate - The acetate form of the 21-substituted-19-nor-progestin telapristone, an orally available selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Upon oral administration, CDB-4124 competitively binds to the progesterone receptor (PR) in progesterone-responsive tissue and inhibits PR-mediated gene expression. This interferes with progesterone activity in the reproductive system. As a result, this agent may suppress ovulation and inhibit proliferation of endometrial tissue. Also, this agent may prevent cell growth and induce apoptosis in estrogen receptor (ER) and PR-positive breast cancer cells through a reduction in progesterone levels, ER downregulation and a suppression of the expression of cyclin-dependent kinases (CDK) 2 and 4, ultimately leading to G1/S cell cycle arrest. Unlike some other SPRMs, this agent does not exert any estrogenic, androgenic, anti-estrogenic, and anti-androgenic activities.

• Telatinib mesylate - The orally bioavailable mesylate salt of the 17-allylaminogeldanamycin (17-AAG) small-molecule inhibitor of several receptor protein tyrosine kinases with potential antiangiogenic and antineoplastic activities. Telatinib binds to and inhibits the vascular endothelial growth factor receptors (VEGFRs) type 2 and 3, platelet-derived growth factor receptor beta (PDGFRb) and c-Kit, which may result in the inhibition of angiogenesis and cellular proliferation in tumors in which these receptors are upregulated. These telatinib-inhibited receptor protein tyrosine kinases are overexpressed or mutated in many tumor cell types and may play key roles in tumor angiogenesis and tumor cell proliferation. 17-AAG is a synthetic analogue of the benzoquinone ansamycin antibiotic geldanamycin and has also been found to inhibit the molecular chaperone Hsp90.

• Telisotuzumab - A monoclonal antibody directed against human hepatocyte growth factor receptor (HGFR or c-Met), with potential antineoplastic activity. Telisotuzumab binds to c-Met, thereby preventing both c-Met binding to its ligand, HGF and the subsequent activation of the HGF/c-Met signaling pathway. This may cause cell death in c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.

• Telisotuzumab vedotin - An antibody-drug conjugate (ADC) composed of telisotuzumab, a monoclonal antibody against the tumor-associated antigen (TAA) and proto-oncogene, c-Met receptor tyrosine kinase (c-Met; MET; hepatocyte growth factor receptor; HGFR) conjugated to the cytotoxic agent monomethyl auristatin E (MMAE) via a valine-citrulline (vc) peptide linker (vc-MMAE; vedotin), with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of telisotuzumab vedotin targets and binds to c-Met expressed on tumor cells. Upon binding, internalization and enzymatic cleavage, the cytotoxic agent MMAE is released into the cytosol. MMAE binds to tubulin and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. This kills the c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis.

• Telomerase inhibitor fj5002 - A derivative of rhodacyanine with potential antineoplastic activity. FJ5002 inhibits telomerase by interfering with holoenzyme assembly and telomere interaction, thus leading to replication-dependent shortening of telomeres with a concurrent increase in aneuploid metaphases and apoptotic cells. Telomerase is active in most tumors cells, but is quiescent in adjacent normal cells.

• Telomerase: 540-548 peptide vaccine - A recombinant peptide consisting of the amino acid residues 540 to 548 of the human telomerase reverse transcriptase (hTERT). Telomerase expression has been directly linked to tumor development; its catalytic subunit is expressed in the majority of human cancer cells, but infrequently in normal cells. Vaccination with telomerase:540-548 peptide may stimulate cytotoxic T cells to recognize and kill telomerase-expressing cells.

• Telomerase-specific type 5 adenovirus obp-301 - A replication-competent oncolytic, telomerase-specific adenovirus serotype 5 (Ad5), with potential antineoplastic activity. OBP-301 contains the human telomerase reverse transcriptase (hTERT) gene promoter sequence that drives the expression of the E1A and E1B genes, and is linked to an internal ribosomal entry site (IRES). Upon administration, OBP-301 selectively infects and replicates in cancer cells that are expressing telomerase, which causes cell lysis. This adenovirus does not infect or replicate in normal, healthy cells. OBP-301 may also potentially be used as a chemosensitizer. hTERT, which encodes for the catalytic protein subunit of telomerase, is overexpressed in a variety of cancer cell types but not in normal, healthy cells. The insertion of an IRES further improves selectivity towards telomerase-expressing cancer cells.

• Teloxantrone - An anthrapyrazole antineoplastic antibiotic. Teloxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis

• Teloxantrone hydrochloride - The hydrochloride salt of an anthrapyrazole antineoplastic antibiotic. Teloxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis

• Telratolimod - A toll-like receptor type 7 and 8 (TLR7/8) agonist with potential immunostimulating and antitumor activities. Upon intratumoral administration, telratolimod binds to and activates TLR7 and 8, thereby stimulating antigen-presenting cells (APCs), including dendritic cells (DCs). Activation of DCs results in the production of proinflammatory cytokines, and the activation of cytotoxic T-lymphocyte (CTL) and B-lymphocyte immune responses. This may cause tumor cell lysis. TLR7 and 8, members of the TLR family, play fundamental roles in the activation of the immune system.

• Temarotene - A synthetic bioactive retinoid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, temarotene binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.

• Temoporfin - A synthetic light-activated chlorin with photodynamic activity. Upon systemic administration, temoporfin distributes throughout the body and is taken up by tumor cells. Upon stimulation of temoporfin by non-thermal laser light (at 652 nm), and in the presence of oxygen, this agent produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to tumor cells. This may kill tumor cells and may reduce the tumor size.

• Temozolomide - A triazene analog of dacarbazine with antineoplastic activity. As a cytotoxic alkylating agent, temozolomide is converted at physiologic pH to the short-lived active compound, monomethyl triazeno imidazole carboxamide (MTIC). The cytotoxicity of MTIC is due primarily to methylation of DNA at the O6 and N7 positions of guanine, resulting in inhibition of DNA replication. Unlike dacarbazine, which is metabolized to MITC only in the liver, temozolomide is metabolized to MITC at all sites. Temozolomide is administered orally and penetrates well into the central nervous system.

• Temsirolimus - An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors.

• Tenalisib - An orally active, highly selective, small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, tenalisib inhibits the PI3K delta and gamma isoforms and prevents the activation of the PI3K/AKT-mediated signaling pathway. This may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. In addition, this agent modulates inflammatory responses through various mechanisms, including the inhibition of both the release of reactive oxygen species (ROS) from neutrophils and tumor necrosis factor (TNF)-alpha activity. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and in inflammatory and autoimmune diseases. By selectively targeting these isoforms, PI3K signaling in normal, non-neoplastic cells is minimally impacted or not affected at all, which minimizes the side effect profile for this agent.

• Tenifatecan - A highly lipophilic preparation of 7-Ethyl-10-hydroxycamptothecin (SN-38) with potential antineoplastic activity. SN2310 is an oil-in-water emulsion of tocopherol covalently linked, via a succinate linker, to SN-38, a synthetic derivative of the cytotoxic alkaloid camptothecin. After succinate linker is hydrolyzed in vivo, the active moiety SN-38 is released and selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-stranded DNA breaks and inducing lethal double-stranded DNA breaks. This inhibits DNA replication and triggers programmed cell death. SN2310 emulsion provides longer circulation time and potentiates drug exposure as compared to the unconjugated SN-38.

• Teniposide - A semisynthetic derivative of podophyllotoxin with antineoplastic activity. Teniposide forms a ternary complex with the enzyme topoisomerase II and DNA, resulting in dose-dependent single- and double-stranded breaks in DNA, DNA: protein cross-links, inhibition of DNA strand religation, and cytotoxicity. This agent acts in the late S or early G phase of the cell cycle.

• Tepoditamab - An immunoglobulin G1 (IgG1) bispecific human monoclonal antibody against human CD3, a T-cell surface antigen, and human C-type lectin domain family 12 member A (CLEC12A), a tumor-associated antigen (TAA) overexpressed on certain tumor cells, with potential antineoplastic activity. Upon administration, tepoditamab binds to both CD3 on T-cells and CLEC12A expressed on malignant cells, such as myeloid blasts, atypical progenitor cells and leukemic stem cells (LSCs). This results in the cross-linking of T-cells with tumor cells, and induces a potent cytotoxic T-lymphocyte (CTL) response against CLEC12A-expressing tumor cells. CLEC12A, a myeloid differentiation antigen and member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily, is overexpressed on myeloid leukemia cells, but not on normal early hematopoietic progenitors, including hematopoietic stem cells (HSCs).

• Tepotinib - An inhibitor of MET tyrosine kinase with potential antineoplastic activity. Tepotinib selectively binds to MET tyrosine kinase and disrupts MET signal transduction pathways, which may induce apoptosis in tumor cells overexpressing this kinase. The receptor tyrosine kinase MET (also known as hepatocyte growth factor receptor or HGFR), is the product of the proto-oncogene c-Met and is overexpressed or mutated in many tumor cell types; this protein plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.

• Teprotumumab - A recombinant, fully human monoclonal antibody directed against the insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Teprotumumab binds to membrane-bound IGF-1R, preventing the binding of the natural ligand IGF-1 and the activation of PI3K/AKT signal transduction; downregulation of the PI3K/AKT survival pathway may result in the induction of apoptosis and decreased cellular proliferation. The activation of IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.

• Terameprocol - A synthetic tetra-methylated derivative of nordihydroguaiaretic acid (NDGA) and transcriptional inhibitor with potential antiviral, antiangiogenic, and antineoplastic activities. Terameprocol competes with the transcription factor Sp1 for specific Sp1 DNA binding domains within gene promoter regions during DNA synthesis. In virally-infected cells, blocking of the Sp1 binding site suppresses Sp1-regulated viral promoter activity and gene expression, thereby inhibiting viral transcription and replication. In tumor cells, blockage of Sp1 binding sites by this agent interferes with the transcription of the Sp1-dependant genes cyclin-dependant kinase (Cdc2), survivin, and vascular endothelial growth factor (VEGF), which are overexpressed in a variety of cancers. By suppressing Sp1-regulated transcription of these genes, terameprocol may reduce tumor angiogenesis and tumor cell proliferation and induce tumor cell apoptosis.

• Terfluranol - A trifluoroethyl derivative with antineoplastic agent.

• Tergenpumatucel-l - An allogeneic lung cancer vaccine with potential immunostimulating and antineoplastic activities. Derived from allogeneic lung tumor cells, tergenpumatucel-L is engineered to express the murine alpha-1,3-galactosyltransferase (GalT), an enzyme humans lack. GalT catalyzes the expression of foreign alpha-1,3-galactosyl (alpha-gal) carbohydrate epitopes in glycoproteins and in glycolipids on the cell membranes of the allogeneic lung tumor cells present in the vaccine, essentially producing a 'xenograft'. The hyperacute rejection involves pre-existing human anti-alpha-gal antibodies that bind the foreign alpha-gal epitopes expressed by the vaccine tumor cell xenograft, resulting in complement-mediated cytotoxicity (CMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) towards endogenous lung tumor cells with unmodified carbohydrate epitopes.

• Teroxirone - A triazene triepoxide with antineoplastic activity. Teroxine alkylates and cross-links DNA, thereby inhibiting DNA replication.

• Tertomotide - A synthetic peptide vaccine, containing 16 amino acid residues (611-626) of the human telomerase reverse transcriptase catalytic subunit (hTERT), with potential antineoplastic activity. Telomerase, a reverse transcriptase normally repressed in healthy cells, is overexpressed in most cancer cells and plays a key role in cellular proliferation. Vaccination with tertomotide may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against telomerase-expressing cells.

• Tesetaxel - A semi-synthetic, orally bioavailable taxane derivative with potential antineoplastic and antiangiogenic properties. Tesetaxel binds to and stabilizes tubulin, promoting microtubule assembly and thereby preventing microtubule depolymerization. This may lead to cell cycle arrest and an inhibition of cell proliferation. This agent may also inhibit pro-angiogenic factors such as vascular endothelial growth factor (VEGF). As it represents poor substrate for P-glycoprotein-related drug resistance mechanisms, this agent may be useful for treating multi-drug resistant tumors.

• Tesevatinib - An orally bioavailable small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Tesevatinib binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including epidermal growth factor receptor (EGFR; ERBB1), epidermal growth factor receptor 2 (HER2; ERBB2), vascular endothelial growth factor receptor (VEGFR), and ephrin B4 (EphB4). This may result in the inhibition of tumor growth and angiogenesis, and tumor regression.

• Tesidolumab - A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the complement pathway protein C5, with complement pathway inhibitory activity and potential immunomodulating activity. Upon administration, tesidolumab targets and binds to C5, thereby preventing both C5 convertase-mediated cleavage of C5 and the formation of C5a and C5b. This inhibits C5-mediated signal transduction, the formation of the membrane attack complex (MAC) and the activation of the terminal complement pathway, and results in the prevention and/or inhibition of both complement-mediated inflammation and cell destruction. C5 plays a key role in the activation of the complement cascade.

• Testolactone - A progesterone derivative with antineoplastic activity. Testolactone inhibits steroid aromatase, thereby preventing the formation of estrogen from adrenal androstenedione and reducing endogenous estrogen levels.

• Tetanus peptide melanoma vaccine - A vaccine consisting of peptides derived from melanoma-associated antigens and a modified T-cell epitope derived from tetanus toxoid. Vaccination with this agent may stimulate a host cytotoxic and helper T-cell response against tumor cells expressing melanoma-associated antigens, resulting in decreased tumor growth.

• Tetanus toxoid vaccine - A preparation of formaldehyde-deactivated toxin isolated from the bacterium Clostridium tetani. Tetanus toxoid is used for booster injection and can stimulate the production of antitoxin antibodies. This agent may be used as an adjuvant in cancer vaccines.

• Tetmyb dna vaccine - A therapeutic engineered DNA vaccine composed of DNA sequences encoding for one or more tetanus toxoid peptides and the oncoprotein MYB, with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, TetMYB is taken up and processed by dendritic cells (DCs), which present the processed antigen to the immune system. This activates cytotoxic T-lymphocytes (CTLs) and causes a CTL-mediated immune response against MYB-expressing tumor cells. MYB, an oncoprotein and transcription factor, is overexpressed in a variety of cancer types and is essential for tumor cell growth, inhibition of differentiation, and protection from apoptosis. Its expression is correlated with lower T-cell infiltration and poorer prognosis. As MYB is only weakly immunogenic, the tetanus toxoid peptides enhance the T-cell mediated immune responses against the MYB-expressing tumor cells.

• Tetradecanoylphorbol acetate - A phorbol ester with potential antineoplastic effects. Tetradecanoylphorbol acetate (TPA) induces maturation and differentiation of hematopoietic cell lines, including leukemic cells. This agent may induce gene expression and protein kinase C (PKC) activity. In addition to potential antineoplastic effects, TPA may exhibit tumor promoting activity.

• Tetrahydrouridine - A synthetic pyrimidine nucleoside analogue with biomodulating activity. Tetrahydrouridine increases the efficacy of the radiosensitizer cytochlor (5-chloro-2'-deoxycytidine) by inhibiting the enzyme deoxycytidine monophosphate (dCMP) deaminase and preventing the premature deamination of the cytochlor metabolite 5-chloro-2'-deoxycytidine monophosphate (CldCMP) to 5-chloro-2'-deoxyuridine monophosphate (CldUMP); in turn, this increases tumor concentrations of CldUMP which is then further anabolized and incorporated selectively into tumor DNA as CldU (5-chloro-2'-deoxyuridine).

• Tetrathiomolybdate - An orally bioavailable metal copper (Cu) chelator, with potential antiangiogenic, anti-metastatic and antitumor activities. Upon oral administration, tetrathiomolybdate (TM) targets and binds to copper and food protein in the gastrointestinal (GI) tract, thereby forming stable complexes and preventing copper uptake and reabsorption. Additionally, absorbed free TM targets and binds to copper and serum albumin in the bloodstream. This depletes systemic copper reserves and deprives the tumor microenvironment (TME) from copper. Chelation of copper by TM downregulates the expression of angiogenic factors of which copper is a cofactor, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and prevents the production of nuclear factor-kappa B (NF-kB). Copper deprivation also inhibits the activity and levels of copper-dependent angiogenic enzymes, such as vascular endothelial growth factor receptor (VEGFR). This modulates the activity of VEGFR-positive endothelial progenitor cells (EPCs) that are necessary for metastasis. EPC deficiency results in the inhibition of angiogenesis and prevents metastasis. TM also inhibits the activities of other copper-containing metalloenzymes, including superoxide dismutase 1 (SOD1) in endothelial cells, cytochrome C oxidase, vascular adhesion protein-1 (VAP-1), antioxidant 1 copper chaperone (ATOX-1) and matrix metalloproteinase 9 (MMP-9). Inhibition of these enzymes interferes with the activation of several signal transduction pathways required for cellular proliferation and angiogenesis. TM also inhibits the activity and levels of lysyl oxidase-like 2 (LOXL2; lysyl oxidase homolog 2), a copper dependent amine oxidase that is critical for modeling the pre-metastatic niche and promotes metastasis, tumor cell migration and invasiveness. In addition, copper depletion also attenuates the activation of host cells within the tumor microenvironment including cancer-associated fibroblasts (CAFs), modulates tumor associated macrophages (TAMs) and promotes cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune responses.

• Tetravalent rna-lipoplex cancer vaccine - A RNA-lipoplex (RNA-LP)-based cancer vaccine containing four naked ribonucleic acid (RNA)-drug products (DPs) RBL001.1, RBL002.2, RBL003.1, and RBL004.1 encoding melanoma-associated antigens (MAAs) encapsulated in liposomes, with potential antineoplastic activity. Upon intravenous administration of the tetravalent RNA-lipoplex cancer vaccine, the liposomes protect the RNA from degradation in the bloodstream, travel to the spleen and are taken up by antigen-presenting cells (APCs); RNA is translocated to the cytoplasm and translated into the four tumor-associated proteins. The expressed proteins are processed and the human leukocyte antigen (HLA)-peptide complexes are presented to the immune system. This induces antigen-specific CD8+ and CD4+ T-cell responses against the four selected MAAs.

• Tezacitabine - A synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.

• Tezacitabine anhydrous - The anhydrous form of tezacitabine, a synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and eventually tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, thereby further inhibiting DNA replication. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates, a necessary step for DNA synthesis, and is overexpressed in many tumor cell types.

• Tf(c)-klh conjugate vaccine - A vaccine containing a clustered pancarcinoma carbohydrate antigen, Thomsen-Friedenreich (TF) antigen, conjugated with keyhole limpet hemocyanin (KLH) with potential antineoplastic activity. TF antigen is a disaccharide epitope (galactose-beta1-3-N-acetylgalactose), normally O-linked to serine or threonine of tumor-associated epithelial mucins. This vaccine contains the TF epitope cluster (c) that is synthesized by linking 3 copies of the TF epitope on a threonine backbone to achieve the essential immunogenic structure. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition. Vaccination with TF(c)-KLH peptide vaccine may produce antibodies and elicit a cytotoxic T lymphocyte (CTL) response against those tumor cells expressing TF antigen, resulting in decreased tumor growth.

• Tgfa-pe38 immunotoxin - A recombinant, chimeric toxin composed of human transforming growth factor alpha (TGF-alpha) fused to a fragment of Pseudomonas exotoxin (PE38) without its cell-binding domain. The TGF-alpha moiety of the agent attaches to tumor cells expressing the epithelial growth factor receptor (EGFR); the exotoxin induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.

• Tgfbdnrii-transduced autologous tumor infiltrating lymphocytes - A preparation of tumor infiltrating lymphocytes (TILs) that are transduced with a retroviral vector encoding a gene for a dominant-negative form of the transforming growth factor beta (TGFb) receptor, TGFbDNRII, with potential immunomodulating activity. Upon administration, the TGFbDNRII-transduced autologous TILs recognize and kill tumor cells. The expression of TGFbDNRII allows for the TILs to be resistant to TGF-b-mediated inhibition of T cell proliferation and activation, which allows optimal TIL activity. The immunosuppressant TGF-b is produced by tumor cells and plays a key role in the repression of the immune system.

• Tgfbeta inhibitor ly3200882 - An orally bioavailable agent that targets transforming growth factor-beta (TGFb), with potential antineoplastic activity. Upon administration, LY3200882 specifically targets and binds to TGFb, which prevents both the binding of TGFb to its receptor TGFbR and TGFb-mediated signal transduction. This may lead to a reduction in TGFb-dependent proliferation of cancer cells. The TGFb signaling pathway is often deregulated in tumors, and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, angiogenesis, and various immune responses.

• Tgf-beta receptor 1 inhibitor pf-06952229 - An orally bioavailable inhibitor of transforming growth factor-beta receptor 1 (TGFbR1), with potential antineoplastic activity. Upon administration, TGF-betaR1 inhibitor PF-06952229 specifically targets and binds to TGFbR1, which prevents TGFbR1-mediated signal transduction. This abrogates TGFbR1-mediated immunosuppression, enhances anti-tumor immunity in the tumor microenvironment (TME) and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGFbR1-dependent proliferation of cancer cells. The TGFb signaling pathway is often deregulated in tumors and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, and angiogenesis. It plays a key role in immunosuppression in the TME.

• Tgf-beta receptor 1 kinase inhibitor sh3051 - An orally bioavailable, small molecule inhibitor of the serine/threonine kinase transforming growth factor-beta (TGF-beta) receptor 1 (TGFbR1; activin receptor-like kinase 5; ALK5), with potential antineoplastic and immunomodulating activities. Upon administration, TGFbR1 inhibitor SH3051 specifically targets and binds to TGFbR1, which prevents TGFbR1-mediated signal transduction. This abrogates TGFbR1-mediated immunosuppression, enhances anti-tumor immunity in the tumor microenvironment (TME) and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGFbR1-dependent proliferation of tumor cells. The TGF-beta signaling pathway is often deregulated in tumors and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, and angiogenesis. It plays a key role in immunosuppression in the TME and cancer cell progression.

• Tgf-beta receptor 1 kinase inhibitor yl-13027 - An orally bioavailable inhibitor of the serine/threonine kinase transforming growth factor-beta receptor 1 (TGFbR1; activin receptor-like kinase 5; ALK5), with potential antineoplastic and immunomodulating activities. Upon administration, TGF-betaR1 inhibitor YL-13027 specifically targets and binds to TGFbR1, which prevents TGFbR1-mediated signal transduction. This abrogates TGFbR1-mediated immunosuppression, enhances anti-tumor immunity in the tumor microenvironment (TME) and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGFbR1-dependent proliferation of cancer cells. The TGFb signaling pathway is often deregulated in tumors and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, and angiogenesis. It plays a key role in immunosuppression in the TME and cancer cell progression.

• Tgfbeta receptor ectodomain-igg fc fusion protein avid200 - A fusion protein composed of the ectodomain of the transforming growth factor (TGF) beta (TGF-beta; TGFb) receptor fused to the human immunoglobulin G (IgG) Fc domain, with potential antineoplastic, immunomodulating and anti-fibrotic activities. Upon administration of the TGFb receptor ectodomain-IgG Fc fusion protein AVID200, the fusion protein specifically and selectively targets, binds to and neutralizes the TGF ligands TGF-beta isoform 1 (TGFb1) and 3 (TGFb3). This prevents TGF ligands from binding to TGF receptors and prevents TGFb-mediated signaling. This abrogates TGFb1/3-mediated immunosuppression, enhances anti-tumor immunity in the tumor microenvironment (TME) and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGFb-dependent proliferation of cancer cells. By preventing TGFb1/3-mediated signaling, AVID200 also prevents bone marrow fibrosis and promotes the proliferation of normal hematopoietic progenitors. TGFb, overproduced in myelodysplastic syndrome (MDS) and in many other types of cancer, plays a key role in immunosuppression in the TME, enhances tumor cell proliferation, and promotes cancer progression. The TGFb1 and TGFb3 isoforms are negative regulators of hematopoiesis that play key roles in the pathogenesis and progression of fibrotic diseases. By selectively targeting only specific isoforms of TGFb with minimal activity against TGFb2, AVID200 minimizes the potential for cardiotoxicity and promotion of metastasis. The TGFb2 isoform promotes hematopoiesis and plays a key role in normal cardiac function while the inhibition of the TGFb2 isoform promotes metastasis.

• Tgf-beta-resistant lmp-specific cytotoxic t-lymphocytes - A preparation of transforming growth factor-beta (TGF-beta)-resistant cytotoxic T-lymphocytes (CTL) reactive to Epstein-Barr virus (EBV) latent membrane proteins 1 and 2 (LMP 1 and 2) with potential antineoplastic activity. T lymphocytes are transduced with a retroviral vector expressing the dominant-negative mutant type II TGF-beta receptor, which blocks signaling by all three TGF-beta isoforms. These TGF-beta-resistant T-lymphocytes are exposed ex-vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding EBV LMP; subsequent exposure to LMP1- or LMP2-expressing lymphoblastoid cell lines is used to expand the CTL. Administered to patients with EBV-positive tumors, TGF-beta-resistant LMP-specific CTL target LMP-positive cells, which may result in a specific CTL response, followed by cell lysis and inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T lymphocyte activation and expansion.

• Thalicarpine - A natural aporphine benzylisoquinoline vinca alkaloid with antineoplastic activity. Thalicarpine binds to and inhibits p-glycoprotein, the multidrug resistance efflux pump. Thalicarpine also induces single-strand breaks in DNA and arrests cancer cells at the G2/M and G1 phase of the cell cycle.

• Thalidomide - A synthetic derivative of glutamic acid (alpha-phthalimido-glutarimide) with teratogenic, immunomodulatory, anti-inflammatory and anti-angiogenic properties. Thalidomide acts primarily by inhibiting both the production of tumor necrosis factor alpha (TNF-alpha) in stimulated peripheral monocytes and the activities of interleukins and interferons. This agent also inhibits polymorphonuclear chemotaxis and monocyte phagocytosis. In addition, thalidomide inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), thereby inhibiting angiogenesis.

• Theramide - A lipophilic disaccharide derivative of muramyl dipeptide (MDP) with strong immunostimulating activity and used as a vaccine adjuvant. MDP, a component of bacterial cell wall, is the minimum chemical structure required for macrophage activation. Due to MDP's toxicity and short duration of action, theramide was developed with improved stability, and can be administered without a liposome carrier. Theramide stimulates macrophage activity, which in turn potentiates other immune responses, including the release of proinflammatory interleukins and tumor necrosis factor alpha (TNF alpha). The release of these cytokines further augments the activation of cellular and humoral immune system.

• Therapeutic angiotensin-(1-7) - A synthetic heptapeptide identical to endogenous angiotensin-(1-7) with vasodilator and antiproliferative activities. Therapeutic angiotensin 1-7 may inhibit cyclooxygenase 2 (COX-2) and the production of proinflammatory prostaglandins and may activate the angiotensin-(1-7) receptor Mas, resulting in diminished tumor cell proliferation. Activation of the angiotensin-(1-7) receptor Mas, a G-protein coupled, seven transmembrane protein, may down-regulate the phosphorylation and activation of Erk1 and Erk2 in the Erk1/Erk2 MAPK signaling pathway. In the renin-angiotensin system, the vasodilating activity of angiotensin- (1-7), hydrolysed from angiotensin II by the type I transmembrane metallopeptidase and carboxypeptidase angiotensin converting enzyme 2 (ACE2) in vivo, counteracts the vasoconstricting activity of angiotensin II.

• Therapeutic autologous dendritic cells - A population of a type of antigen-presenting cell (APC), the dendritic cell (DC), harvested from a patient and grown in vitro in the presence of tumor-associated antigens (TAAs) derived from the patient's tumor (a technique known as 'pulsing') and then injected back into the patient; autologous DCs so manipulated may stimulate a specific cell-mediated antitumoral cytotoxicity. DCs derived from a patient may also be fused with the patient's tumor cells in vitro to combine sustained tumor antigen expression with the antigen-presenting and immunostimulatory capacities of DCs; when injected back into the patient, these autologous DC-tumor cell hybrids (fusion cells) may stimulate an active antitumoral immune response.

• Therapeutic breast/ovarian/prostate peptide cancer vaccine dpx-0907 - A lipid-based multi-peptide cancer vaccine targeted against multiple cancers with immunopotentiating activity. Therapeutic breast/ovarian/prostate peptide cancer vaccine DPX-0907 is a lyophilized liposomal proprietary preparation comprised of 7 tumor-specific HLA-A2-restricted epitopes (TAAs): Topoisomerase II alpha, B-cell receptor-associated protein 31 (CDM protein), TNF-alpha-converting enzyme (TACE/ADAM17), Abelson homolog 2 (Abl2), gamma catenin (Junction plakoglobin), epithelial discoidin domain receptor 1 (EDDR1) and integrin beta 8 subunit. Upon vaccination, the lyophilized antigen/adjuvant/liposome complex is re-suspended in Montanide 1SA51 VG to create a depot effect, thereby presenting the TAAs to the immune system for a prolonged period of time. This may stimulate a potent cytotoxic T-lymphocyte (CTL) immune response against cancer cells that express these 7 TAAs and share epitopes with the vaccine epitope peptides, resulting in tumor cell lysis. The 7 TAAs are overexpressed on the surface of breast/ovarian and prostate cancer cells and play an important role in tumor cell growth and survival.

• Therapeutic cancer vaccine atp128 - A self-adjuvanted chimeric recombinant protein vaccine, based on the self-adjuvanting KISIMA immunization platform, composed of three components: the 42 residue fragment Z12, a cell penetrating peptide (CPP) derived from the ZEBRA protein transduction domain, a toll-like receptor (TLR) peptide agonist as an adjuvant and a chimeric cargo, a multiple antigenic domain (MAD; MultiE), that contains an as of yet not disclosed amount of major histocompatibility class (MHC)-restricted peptides derived from as of yet undisclosed tumor-associated antigens (TAAs) that are specific for colorectal cancer (CRC) patients, with potential immunomodulating and antineoplastic activities. Upon administration of ATP128, the Z12 moiety targets, binds to and penetrates antigen-presenting cells (APCs), specifically dendritic cells (DCs) and promotes the loading of the epitopes into the DCs and transports antigenic cargoes into both endosomal and cytosolic compartments. Upon processing and antigen presentation by MHC II and I, the immune system is stimulated and activates specific CD4+ and CD8+ T-cells, respectively, against the multi-epitopes specific for the CRC cells, thereby killing the CRC cells.

• Therapeutic dendritic cells/cytokine-induced killer cells - A preparation of autologous dendritic cells (DC) mixed with cytokine-induced killer (CIK) cells (DC-CIK), with potential immunopotentiating and antineoplastic activities. DCs were obtained ex vivo by incubation of peripheral blood lymphocytes (PBLs) with granulocyte-macrophage colony-stimulating factor stimulating factor (GM-CSF or CSF2), tumor necrosis factor (TNF), and interleukin (IL)-24 and were sensitized with tumor-associated antigens (TAAs). Cytokine-induced killer (CIK) cells are immune effector cells with both T-cell and natural killer (NK) cell like phenotype. CIKs are non-major histocompatibility complex (MHC)-restricted, NK-like T-lymphocytes, which express both CD3, a T-cell surface marker, and CD56, a natural killer cell surface marker, and have been generated ex vivo by incubation of peripheral blood lymphocytes (PBLs) with anti-CD3 monoclonal antibody, IL-2, IL-1 alpha, and interferon gamma (IFN-gamma) and then expanded. Upon co-culture of DCs and CIKs, and administration of DC-CIK cells into the patient, the DCs are able to stimulate the immune response to exert a specific anti-tumor immune response, while the CIK cells exert direct oncolytic activity.

• Therapeutic ex vivo-expanded allogeneic gamma delta t-cells - An off-the-shelf preparation of a subset of therapeutic, ex vivo-expanded, allogeneic T-lymphocytes that express only gamma chain and delta chain T-cell receptors (TCRs), with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic ex vivo-expanded allogeneic gamma delta T-cells, these cells secrete interferon-gamma (IFN-g) and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.

• Therapeutic ex-vivo-treated autologous central memory t cells - A preparation of autologous ex-vivo treated central memory T (Tcm) cells with potential immunostimulatory activity. Upon isolation and ex-vivo treatment through as an of yet not elucidated method, the therapeutic ex-vivo-treated autologous Tcm cells, upon reintroduction into the patient, can activate an antitumor immune response which may eradicate tumor cells.

• Therapeutic gamma delta t-lymphocytes - A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.

• Therapeutic invariant natural killer t-cells - A preparation of natural killer T-cells (NKTs) expressing an invariant (alpha, beta) T-cell receptor (iNKTs), with potential immunomodulating and antineoplastic activities. Upon infusion of the therapeutic iNKTs, these cells recognize CD1d-restricted lipid ligands, which are expressed on certain tumor cells, and secrete large amounts of various cytokines. This may activate the immune system against tumor cells. Additionally, iNKTs directly target and lyse tumor cells.

• Therapeutic liver cancer peptide vaccine ima970a - An off-the-shelf hepatocellular cancer (HCC) multi-peptide-based therapeutic vaccine composed of sixteen peptides derived from tumor-associated antigens (TAAs) expressed by hepatic tumor cells, of which seven are restricted to human leukocyte antigen (HLA)-A2 (HLA-A*02), five to HLA-A*24 and four to HLA class II, with potential immunomodulating and antineoplastic activities. Upon intradermal administration of the therapeutic liver cancer peptide vaccine IMA970A, the liver-specific peptides in the vaccine activate the immune system to exert both CD4+ T-helper and CD8+ cytotoxic T-lymphocyte (CTL)-mediated immune responses against liver cancer cells.

• Therapeutic tumor infiltrating lymphocytes - A preparation of cells, consisting of autologous tumor infiltrating lymphocytes, that are manipulated in vitro and, upon administration in vivo, re-infiltrate the tumor to initiate tumor cell lysis. In vitro, therapeutic tumor-infiltrating lymphocytes (TILs) are isolated from tumor tissue and cultured with lymphokines such as interleukin-2; the therapeutic TILs are then infused into the patient, where, after re-infiltration of the tumor, they may induce lysis of tumor cells and tumor regression. The use of therapeutic TILs is considered a form of adoptive immunotherapy.

• Thiarabine - A analog of antimetabolite cytarabine (ara-C), with potential antineoplastic activity. Upon administration, thiarabine (T-araC) is phosphorylated to the triphosphate form T-araCTP and competes with cytidine for incorporation into DNA. This results in an inhibition of DNA replication and RNA synthesis, chain termination and may eventually decrease tumor cell proliferation. Compared to ara-C, T-araC appears to have a longer half-life and has a higher efficacy.

• Thiodiglycol - A hydrolysis product of mustard gas, an alkylating agent, with antineoplastic activity.

• Thioguanine - A synthetic guanosine analogue antimetabolite. Phosphorylated by hypoxanthine-guanine phosphoribosyltransferase, thioguanine incorporates into DNA and RNA, resulting in inhibition of DNA and RNA syntheses and cell death. This agent also inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase, thereby inhibiting purine synthesis.

• Thioguanine anhydrous - The anhydrous salt form of thioguanine, a synthetic guanosine analogue antimetabolite, with antineoplastic activity. Thioguanine is phosphorylated by hypoxanthine-guanine phosphoribosyltransferase to 6-thioguanylic acid (TGMP) and upon conversion to thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP), this agent is incorporated into DNA and RNA, resulting in inhibition of DNA and RNA synthesis and cell death. This agent also inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase, thereby inhibiting purine ribonulceotide synthesis.

• Thioinosine - A sulfhydryl analog of inosine and an antimetabolite with potential antineoplastic and immunosuppressive properties. Thioinosine interferes with de novo purine synthesis and perturbs the pool of nucleotides necessary for DNA replication. As a result, this agent inhibits DNA synthesis, blocks cellular proliferation and induces apoptosis.

• Thioredoxin-1 inhibitor px-12 - An orally bioavailable small molecule with potential antineoplastic activity. Thioredoxin-1 inhibitor PX-12 irreversibly binds to thioredoxin-1 (Trx-1) and inhibits its activity, which may result in growth inhibition and the induction of apoptosis. Overexpressed in many cancer cell types, the low molecular weight redox protein Trx-1 regulates transcription factor activity and inhibits apoptosis, promoting cell growth and survival; it also interacts with growth factors extracellularly to stimulate cell growth.

• Thiotepa - A polyfunctional, organophosphorus alkylating agent and a stable derivative of N,N',N-triethylenephosphoramide (TEPA), with antineoplastic activity. Upon administration, thiotepa is converted into highly reactive ethylenimine groups, which covalently bind to nucleophilic groups in DNA and demonstrate a preference for the N7 position of guanine bases. This induces crosslinking of alkylated guanine bases in double-stranded DNA, interferes with both DNA replication and cell division, and results in both the induction of apoptosis and the inhibition of cell growth.

• Thioureidobutyronitrile - A water-soluble, small molecule and activator of the tumor suppressor protein p53, with potential antineoplastic activity. Upon intravenous administration, thioureidobutyronitrile activates p53 which in turn induces the expressions of p21 and PUMA (p53 up-regulated modulator of apoptosis), thereby inhibiting cancer cell growth and causing tumor cell apoptosis. Thioureidobutyronitrile may be effective in drug-resistant cancers with mutated p53. p53 tumor suppressor, a transcription factor regulating the expression of many stress response genes and mediating various anti-proliferative processes, is often mutated in cancer cells.

• Thl-p - A proprietary, oral Chinese medicinal herb preparation with potential antioxidant, immunomodulating, and antineoplastic activities. THL-P (Tien-Hsien Liquid-P) contains fourteen Chinese medicinal herbs including: Cordyceps sinensis, Oldenlandia diffusa, Indigo pulverata levis, Polyporus umbellatus, Radix astragali, Panax ginseng, Solanum nigrum L., Pogostemon cablin, Atractylodis macrocephalae rhizoma, Trichosanthes radix, Clematis radix, Margarite, Ligustrum lucidum Ait and Glycyrrhiza radix. Administered as an oral liquid, THL-P may modulate the activity of natural killer (NK) cells, cytotoxic T-lymphocytes (CTLs), macrophages and polymorphonuclear leukocytes, and enhance the secretion of interleukins (ILs) and interferon-gamma (IFN-gamma). This agent may also induce G2/M cell cycle arrest and downregulate several important oncogenic signaling pathways.

• Thorium th 227 anetumab corixetan - A radioimmunoconjugate consisting of anetumab, a human immunoglobulin G1 (IgG1) monoclonal antibody directed against the cell surface glycoprotein mesothelin, conjugated to the chelating agent corixetan, and labeled with the alpha-emitting radioisotope thorium Th 227, with potential antineoplastic activity. Upon administration of thorium Th 227 anetumab corixetan, the anetumab moiety binds to the tumor-associated antigen (TAA) mesothelin, delivering a cytotoxic dose of alpha radiation to cells expressing mesothelin.

• Thorium th 227 anti-her2 monoclonal antibody bay2701439 - A radioimmunoconjugate consisting of a monoclonal antibody targeting the tyrosine kinase receptor epidermal growth factor receptor 2 (HER2; ErbB2) and labeled with the alpha-emitting radioisotope thorium Th 227, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of BAY2701439 targets and specifically binds to HER2 on tumor cells, delivering a cytotoxic dose of alpha radiation to cells expressing HER2. HER2 is overexpressed in a variety of cancer cell types and is associated with increased tumor cell proliferation.

• Thorium th 227 anti-psma monoclonal antibody bay 2315497 - A radioimmunoconjugate consisting of a monoclonal antibody targeting the tumor-associated antigen (TAA) human prostate-specific membrane antigen (PSMA) and labeled, via a 3-hydroxypyridin-2-one (3,2-HOPO) chelator, with the alpha-emitting radioisotope thorium Th 227, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of BAY 2315497 targets and specifically binds to PSMA on tumor cells, delivering a cytotoxic dose of alpha radiation to cells expressing PSMA. PSMA is overexpressed on the surface of metastatic and hormone-refractory prostate cancer cells.

• Threonine tyrosine kinase inhibitor cfi-402257 - An orally bioavailable, selective inhibitor of the dual specificity protein kinase TTK (monopolar spindle 1 kinase, Mps1), with potential antineoplastic activity. Upon administration, the Mps1 inhibitor CFI-402257 selectively binds to and inhibits the activity of Mps1. This inactivates the spindle assembly checkpoint (SAC) and accelerates mitosis, which results in chromosomal misalignment and missegregation, and mitotic checkpoint complex destabilization. This induces cell death in Mps1-overexpressing cancer cells. Mps1, a tyrosine and serine/threonine kinase expressed in proliferating normal tissues, is essential for proper SAC functioning and chromosome alignment. Overexpressed in various human tumors, Mps1 plays a key role in uncontrolled tumor cell growth.

• Thymidylate synthase inhibitor cx1106 - A thymidylate synthase (TS) inhibitor with potential antineoplastic activity. Upon administration, TS inhibitor CX1106 binds to and inhibits TS. This reduces thymine nucleotide synthesis, inhibits DNA synthesis and cell division, causes DNA damage and leads to tumor cell apoptosis. TS catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), an essential precursor for DNA synthesis, and plays a key role in cell growth and division.

• Thymidylate synthase inhibitor dfp-11207 - An orally available thymidylate synthase (TS) inhibitor with potential antineoplastic activity. Upon oral administration, DFP-11207 binds to and inhibits TS. This reduces thymine nucleotide synthesis, inhibits DNA synthesis and cell division, causes DNA damage and leads to tumor cell apoptosis. TS catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).

• Thymopentin - A synthetic pentapeptide which is the active site of the naturally occurring hormone thymopoietin with immunomodulating properties. Thymopentin enhances the production of thymic T cells and may help restore immunocompetence in immunosuppressed subjects. This agent also augments the effects of ionizing radiation by arresting cancer cells in the G2/M phase of the cell cycle.

• Tiazofurin - A synthetic nucleoside analogue with antineoplastic activity. Tiazofurin (TR) is anabolized intracellularly to an analogue of NAD, tiazole-4-carboxamide adenine dinucleotide (TAD), a potent inhibitor of IMP dehydrogenase (IMPDH); IMPDH is the rate-limiting enzyme for de novo purine synthesis. Inhibition of IMPDH results in reduced levels of guanylates, resulting in the inhibition tumor cell growth in vitro and in vivo.

• Tidutamab - A humanized, Fc domain-containing, bispecific monoclonal antibody targeting human CD3, a T-cell surface antigen, and somatostatin receptor 2 (SSTR2), a tumor-associated antigen (TAA) expressed on certain cancer cells, with potential antineoplastic activity. Upon administration, tidutamab binds to both T-cells and SSTR2-expressing cancer cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against the SSTR2-expressing cancer cells. The inclusion of an Fc domain on the antibody prolongs the half-life of the bispecific antibody.

• Tigapotide - A synthetic 15-mer peptide corresponding to amino acids 31-45 of the 94-amino acid isoform of human prostate secretory protein (PSP-94) with potential anti-metastasis and anti-angiogenesis activities. PSP-94-derived peptide PCK3145 may inhibit the secretion of the metastasis-related protein matrix metalloproteinase-9 (MMP-9) and its potential binding to its cell surface receptor CD44; may interfere with the vascular endothelial growth factor (VEGF) signaling pathway, resulting in an anti-angiogenesis effect; and may reduce the levels of parathyroid hormone-related protein (PTHrP), decreasing plasma calcium levels. PSP-94, one of three predominant proteins found in seminal fluid, may be down-regulated in prostate cancer, representing a potential survival mechanism for prostate cancer cells. MMP-9 is implicated in the invasion and metastasis of cancer. PTHrP may be expressed by various tumor cell types, resulting in the hypercalcemia of malignancy.

• Tigatuzumab - A humanized agonistic monoclonal antibody directed against human tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) with potential antitumor activity. Mimicking the natural receptor ligand TRAIL, tigatuzumab binds to TRAIL-R2, activating signal transduction pathways that may result in tumor cell apoptosis and a reduction in tumor growth. A member of the tumor necrosis factor (TNF) receptor family, TRAIL-R2, also known as DR5 (death receptor 5), is expressed on the surfaces of many types of malignant cells.

• Tigit inhibitor m6223 - An inhibitor of T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), a co-inhibitory molecule and immune checkpoint inhibitor, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, TIGIT inhibitor M6223 targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs), thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PRR2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8+ T-cells. This leads to CD226 dimerization and CD226-mediated signaling and activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family (IgSF) and an immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.

• Til 1383i t cell receptor-transduced autologous t cells - Autologous peripheral blood lymphocytes-derived T cells transduced with a retroviral encoding TIL 1383I, a T cell receptor (TCR) specific for melanoma antigen tyrosinase, with potential immunostimulating and antineoplastic activity. After transduction, expansion in culture, and reintroduction into the patient, TIL 1383I TCR-transduced autologous T cells bind to tumor cells expressing tyrosinase, which may induce cytokine expression, activation and proliferation of T-cells, and a specific cytotoxic T-lymphocyte (CTL) response against tyrosinase-expressing tumor cells. TIL 1383I TCR originated from a melanoma patient's CD4+ tumor-infiltrating lymphocytes and is reactive against a class I MHC (HLA-A2)-restricted epitope (368-376) of tyrosinase.

• Tilarginine - A pan-nitric oxide synthase (NOS) inhibitor, with potential immunomodulating and antineoplastic activities. Upon administration, tilarginine binds to and inhibits NOS, a free radical signaling molecule that promotes angiogenesis, metastasis, and immunosuppression in the tumor microenvironment (TME). Reduction in NOS activity may abrogate the immunosuppressive TME, enhance tumor antigen-specific immune response and inhibit tumor cell proliferation.

• Tilogotamab - An agonistic hexamer formation-enhanced mixture of two antibodies (HexaBody) that target two separate epitopes on death receptor type 5 (DR5; TNFRSF10B; tumor necrosis factor-related apoptosis-inducing ligand receptor 2; TRAILR2), with potential antineoplastic activity. Upon administration, tilogotamab specifically binds to and activates DR5. This results in the activation of caspase cascades and the induction of apoptosis in DR5-expressing tumor cells. DR5, a cell surface receptor and member of the tumor necrosis factor receptor superfamily (TNFRSF), is involved in the promotion of caspase-dependent apoptosis. Compared to other DR5 antibody-based agonists, the antibodies in GEN1029 (DR5-01 and DR5-05) elicit increased receptor activation because they exhibit enhanced formation of antibody hexamers and receptor clusters at the cell surface due to E430G mutations in the Fc domains of both antibodies.

• Tilsotolimod sodium - A proprietary synthetic oligonucleotide-based agonist of toll-like receptor 9 (TLR9), with potential immunostimulating activity. Upon administration, TLR9 agonist IMO-2125 binds to and activates TLR9 expressed by plasmacytoid dendritic cells (pDCs) and B-cells. This initiates immune signaling pathways, activates B-cells and pDCs, and induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.

• Timonacic - A cyclic sulfur amino acid derivative with potential antineoplastic and antioxidant activities. Acting on cellular membranes of malignant cells through an unknown mechanism, timonacic may induce malignant cells to revert back to an untransformed state. This agent may also restore contact inhibition, a phenomenon characterized by the paracrine inhibition of mitosis following the formation of a critical cell mass, presumably the result of cell-to-cell signal transfer. Timonacic may also produce antioxidant effects secondary to its release of cysteine and restoration of glutathione concentrations.

• Tin ethyl etiopurpurin - A synthetic purpurin with photosensitizing activity. Tin ethyl etiopurpurin preferentially accumulates in tumor cells due to an increased rate of metabolism. Upon exposure to a light source, this agent absorbs light, forming an extended high energy conformational state that produces high quantum yields of singlet oxygen with local cytotoxic effects.

• Tinostamustine - An alkylating histone-deacetylase inhibitor (HDACi) fusion molecule composed of the alkylating agent bendamustine fused to the pan-HDACi vorinostat, with potential bi-functional antineoplastic activity. Upon administration of tinostamustine the vorinostat moiety targets and binds to HDACs. This leads to an accumulation of highly acetylated histones, which results in an induction of chromatin remodeling, a modulation of gene expression, an inhibition of tumor cell division and the induction of tumor cell apoptosis. The bendamustine moiety binds to, alkylates and crosslinks macromolecules, inhibiting DNA, RNA and protein synthesis, which also results in tumor cell apoptosis. Thus, tinostamustine shows superior efficacy compared to the activity of either agent alone. In addition, the inhibition of HDAC6 activity by tinostamustine induces the activation of inositol-requiring enzyme 1 (IRE-1), the key regulatory protein for the unfolded protein response (UPR). Induction of the UPR increases the sensitivity of certain cancer cell types to certain chemotherapeutic agents, such as proteasome inhibitors. Therefore, tinostamustine may work synergistically with proteasome inhibitors. HDACs, enzymes that deacetylate chromatin histone proteins, are overexpressed in various cancers and play a key role in proliferation and resistance of tumor cells.

• Tinzaparin sodium - The sodium salt of a low molecular weight heparin (LMWH), obtained by controlled enzymatic depolymerization of heparin from porcine intestinal mucosa, with antithrombotic properties. Tinzaparin is a potent inhibitor of several activated coagulation factors, especially Factors Xa and IIa (thrombin); its primary activity is mediated through the plasma protease inhibitor antithrombin. In addition, this agent may inhibit angiogenesis through: 1) competitive binding of the heparin-binding sites on endothelial cells for the proangiogenic cytokines vascular endothelial growth factor (VEGF) and beta-fibroblast growth factor (beta-FGF) and 2) increasing the release of tissue factor pathway inhibitor (TFPI), a negative regulator of angiogenesis.

• Tiomolibdate choline - An orally active second generation tetrathiomolybdate analog with anti-angiogenic and antineoplastic activities. Tiomolibdate choline selectively chelates the copper ion in superoxide dismutase 1 (SOD1) in endothelial cells, thereby depleting SOD1 of copper and inhibiting its activity. Inhibition of SOD1 interferes with the activation of several signal transduction pathways required for cellular proliferation and angiogenesis, including those mediated by ERK1/2 and FAK and Src kinases. This results in an inhibition of cell proliferation and angiogenesis as well as induction of apoptosis.

• Tiomolibdate diammonium - An ammonium salt with potential antiangiogenic and antitumor activities. Tetrathiomolybdate has been found to deplete systemic copper reserves through an unknown mechanism. This agent has been shown to inhibit the activities of cuproenzymes, including superoxide dismutase 1 (SOD1) and cytochrome c oxidase (COX), which may contribute to its antiangiogenic and antitumor effects.

• Tipapkinogene sovacivec - A cancer vaccine comprised of a modified, replication-defective, vaccinia virus Ankara (MVA) strain encoding the tumor-associated antigens (TAAs) human papillomavirus type 16 (HPV16) subtypes E6 and E7, and human interleukin-2 (IL-2), with potential immunostimulating and antineoplastic activities. Vaccination with tipapkinogene sovacivec stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing HPV16 E6 and E7, resulting in tumor cell lysis. Expression of IL-2 augments the specific CTL response against HPV16 E6- and E7-expressing tumor cells.

• Tipifarnib - A nonpeptidomimetic quinolinone with potential antineoplastic activity. Tipifarnib binds to and inhibits the enzyme farnesyl protein transferase, an enzyme involved in protein processing (farnesylation) for signal transduction. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis.

• Tirabrutinib - An orally available formulation containing an inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, tirabrutinib covalently binds to BTK within B cells, thereby preventing B cell receptor signaling and impeding B cell development. As a result, this agent may inhibit the proliferation of B cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

• Tiragolumab - A human monoclonal antibody targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory activity. Upon administration, tiragolumab binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs), thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8+ T-cells, and leads to CD226 dimerization and CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family and immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.

• Tirapazamine - A benzotriazine di-N-oxide with potential antineoplastic activity. Tirapazamine is selectively activated by multiple reductases to form free radicals in hypoxic cells, thereby inducing single-and double-strand breaks in DNA, base damage, and cell death. This agent also sensitizes hypoxic cells to ionizing radiation and inhibits the repair of radiation-induced DNA strand breaks via inhibition of topoisomerase II.

• Tirbanibulin - An orally bioavailable small molecule Src kinase inhibitor with potential antineoplastic activity. Unlike other Src kinase inhibitors which bind to the ATP-binding site, tirbanibulin specifically binds to the peptide substrate binding site of Src kinase; inhibition of kinase activity may result in the inhibition of primary tumor growth and the suppression of metastasis. Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis.

• Tisagenlecleucel - Autologous T-lymphocytes transduced with a modified lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) and the zeta chain of the TCR/CD3 complex (CD3-zeta), coupled to the signaling domain of 4-1BB (CD137), with potential immunomodulating and antineoplastic activities. Upon transfusion, tisagenlecleucel directs the T-lymphocytes to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19 and the inclusion of this signaling domain may increase the antitumor activity compared to the inclusion of the CD3-zeta chain alone. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CD3-zeta (or CD247) is a transmembrane signaling adaptor polypeptide that regulates the assembly of complete TCR complexes and their expression on the cell surface.

• Tislelizumab - A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, tislelizumab binds to PD-1 and inhibits the binding of PD-1 to the PD-1 ligands programmed cell death-1 ligand 1 (PD-L1), and PD-1 ligand 2 (PD-L2). This prevents the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of both T-cells and T-cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin (Ig) superfamily expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligands; it plays an important role in tumor evasion from host immunity.

• Tisotumab vedotin - An antibody-drug conjugate (ADC) comprised of tisotumab, a monoclonal antibody against human tissue factor (TF) covalently coupled, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antiangiogenic, anticoagulant and antineoplastic activities. Upon administration of tisotumab vedotin, the tisotumab moiety binds to cell surface TF and is internalized. Tisotumab binds to factor VIIa (FVIIa), which interferes with the activation of factor X (FX) into FXa. This may prevent thrombin formation and cancer-associated venous thromboembolism, and may inhibit angiogenesis and tumor cell proliferation. After internalization of the agent, the MMAE moiety is released by proteolytic cleavage. It then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. TF, a transmembrane protein and initiator of the coagulation cascade, is overexpressed in many tumor cells and tumor-resident endothelial cells. Expression of TF is correlated with metastasis, angiogenesis, tumor cell growth and tumor-associated thrombosis.

• Tivantinib - An orally bioavailable small molecule inhibitor of c-Met with potential antineoplastic activity. c-Met inhibitor ARQ 197 binds to the c-Met protein and disrupts c-Met signal transduction pathways, which may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein, the product of the proto-oncogene c-Met, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.

• Tivozanib - An orally bioavailable inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 with potential antiangiogenic and antineoplastic activities. Tivozanib binds to and inhibits VEGFRs 1, 2 and 3, which may result in the inhibition of endothelial cell migration and proliferation, inhibition of tumor angiogenesis and tumor cell death. VEGFR tyrosine kinases, frequently overexpressed by a variety of tumor cell types, play a key role in angiogenesis.

• Tlc ell-12 - A liposomal formulation of the ether lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine with potential antineoplastic activity. TLC ELL-12 induces tumor cell apoptosis via mitochondria- and caspase-mediated mechanisms. Liposomal encapsulation reduces the free agent's hemolytic toxicity.

• Tlr agonist bdb001 - A toll-like receptor (TLR) agonist with potential immunostimulating and antineoplastic activities. Upon administration, TLR agonist BDB001 activates one or more not yet disclosed TLRs, which may result in macrophage and plasmacytoid dendritic cell (pDC) stimulation; secretion of interferon alpha (IFNa); production of proinflammatory cytokines; upregulation of co-stimulatory molecules; enhanced T- and B-cell stimulatory responses; T-cell proliferation; and a T-helper 1 (Th1) immune response. TLRs are transmembrane receptors that recognize structurally conserved microbial molecules such as bacterial cell-surface lipopolysaccharides (LPS), lipoproteins, lipopeptides, lipoarabinomannan and flagellin, among others; immune responses stimulated by TLR activation may result in immune-mediated tumor cell killing.

• Tlr agonist bsg-001 - A toll-like receptor (TLR) agonist with potential immunomodulating and antineoplastic activities. Upon inhalation, TLR agonist BSG-001 activates one or more not yet disclosed TLRs, which may result in macrophage and plasmacytoid dendritic cell (pDC) stimulation, secretion of interferon alpha (IFNa), production of proinflammatory cytokines, upregulation of co-stimulatory molecules, enhanced T- and B-cell stimulatory responses, T-cell proliferation and a T-helper 1 (Th1) immune response. TLRs are transmembrane receptors that recognize structurally conserved microbial molecules such as bacterial cell-surface lipopolysaccharides (LPS), lipoproteins, lipopeptides, lipoarabinomannan and flagellin, among others. Immune responses stimulated by TLR activation may result in immune-mediated tumor cell killing.

• Tlr agonist cadi-05 - A poly-Toll-like receptor (TLR) agonist polyantigenic vaccine containing heat killed Mycobacterium indicus pranii (Mycobacterium w or Mw) with potential immunostimulating and antineoplastic activities. Upon administration, poly-TLR agonist polyantigenic vaccine activates a number of TLRs, which may result in macrophage and plasmacytoid dendritic cell (pDC) stimulation; secretion of interferon alpha; production of pro-inflammatory cytokines; upregulation of co-stimulatory molecules, enhanced T and B-cell stimulatory responses; T cell proliferation, and a Th1 immune response. TLRs are transmembrane receptors that recognize structurally conserved microbial molecules such as bacterial cell-surface lipopolysaccharides (LPS), lipoproteins, lipopeptides, lipoarabinomannan and flagellin, among others; immune responses stimulated by TLR activation may result in antineoplastic effects.

• Tlr7 agonist 852a - A synthetic imidazoquinoline Toll-like receptor 7 (TLR7) agonist with immunostimulating and potential antitumor activities. TLR7 agonist 852A binds to and activates TLR7, thereby stimulating plasmacytoid dendritic cells (pDC) through the TLR7-MyD88-dependent signaling pathway. Activation of pDC results in secretion of interferon alpha, the production of proimflammatory cytokines, the upregulation of co-stimulatory molecules, and enhanced T and B-cell stimulatory responses.

• Tlr7 agonist bnt411 - A Toll-like receptor (TLR) 7 agonist with potential immunostimulating and antitumor activities. Upon administration, TLR7 agonist BNT411 binds to and activates TLR7. This may trigger, in addition to other possible responses, the activation of cluster of differentiation (CD) 8+ T cells, B cells, and innate immune cells including natural killer (NK) cells and macrophages. TLR7 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.

• Tlr7 agonist lhc165 - A benzonapthyridine Toll-like receptor (TLR) 7 agonist that is adsorbed to aluminum hydroxide with immunostimulating and potential antitumor activities. Upon intratumoral administration of TLR7 agonist LHC165, the agent is slowly released and targets, binds to and activates TLR7. This may trigger, in addition to other possible responses, the activation of cluster of differentiation (CD) 8+ T cells and natural killer (NK) cells, the blockage of the suppressive function of regulatory T cells (Tregs), and the production of interferon alpha (IFNa). TLR7 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.

• Tlr-directed cationic lipid-dna complex jvrs-100 - A cationic lipid DNA complex (CLDC) consisting of DOTIM/cholesterol liposomes and plasmid DNA, containing immunostimulatory CpG and non-CpG motifs, with potential immunostimulating and antineoplastic activities. Upon systemic administration, TLR-directed cationic lipid-DNA complex JVRS-100 enters dendritic cells (DCs) and macrophages; immunostimulatory DNA binds to and activates Toll-like receptors (TLRs), which may result in the generation of anti-tumor natural killer (NK) cell and T-cell responses by the innate immune system. In addition, as a vaccine adjuvant, this agent may induce a strong cytotoxic T-lymphocyte (CTL) response to co-administered antigen.

• Tm4sf1-car/epcam-car-expressing autologous t cells - A mixed preparation of allogeneic T-lymphocytes that have been genetically modified to express either a chimeric antigen receptor (CAR) specific for the antigen transmembrane 4 L six family member 1 (TM4SF1) (CART-TM4SF1) or a CAR specific for epithelial cell adhesion molecule (EpCAM) (CART-EpCAM), with potential immunostimulating and antineoplastic activities. Upon administration of the TM4SF1-CAR/EpCAM-CAR-expressing autologous T cells, the TM4SF1-CAR-expressing autologous T-cells specifically recognize and bind to TM4SF1-expressing tumor cells and the EpCAM-CAR-expressing autologous T-cells specifically recognize and bind to EpCAM-expressing tumor cells, resulting in tumor cell lysis. TM4SF1 and EpCAM are expressed by a variety of tumor cells.

• Tn(c)-klh conjugate vaccine - A vaccine containing a clustered pancarcinoma carbohydrate antigen conjugated with keyhole limpet hemocyanin (KLH) with potential antineoplastic activity. Alpha-N-acetylgalactosamine (Tn) is a monosaccharide usually O-linked to serine or threonine residues of mucins found on most epithelial cancers with the highest expression on prostate cancer. This vaccine contains the Tn epitope cluster (c) that is synthesized by linking 3 copies of the Tn epitope on a threonine backbone to achieve the essential immunogenic structure. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition. Vaccination with Tn(c)-KLH vaccine may produce antibodies and elicit a cytotoxic T lymphocyte (CTL) response against those tumor cells expressing Tn antigen, resulting in decreased tumor growth.

• Tnf transduced til - A preparation of autologous tumor-infiltrating lymphocytes (TILs) that have been transduced with a retroviral vector encoding the gene for tumor necrosis factor (TNF), a cytokine with anti-angiogenic and cytotoxic activity. Following genetic modification, the lymphocytes are returned to the patient, infiltrate the tumor site, and deliver TNF directly to the tumor site, thereby exerting a specific antitumor effect, and avoiding TNF-related systemic toxicity.

• Tnfalpha/il-2-encoding oncolytic adenovirus tilt-123 - A genetically-engineered, replication competent, oncolytic serotype 5/3 capsid-modified adenovirus and encoding for the T-cell immunostimulatory cytokines tumor nerosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2), with potential oncolytic and immunostimulating activities. Upon administration of TNFalpha/IL-2-encoding oncolytic adenovirus TILT-123, the oncolytic adenovirus binds to specific Ad3 receptors that are highly expressed on certain tumor cells and selectively infect and replicate in tumor cells, and express TNF-alpha and IL-2. The oncolytic virus itself induces a viral-mediated tumor cell lysis which may result in the activation of a systemic immune response against tumor-associated antigens. The expressed proteins may further stimulate the immune system to modify the immunosuppressive tumor microenvironment (TME) and induce a cytotoxic T-lymphocyte (CTL) response against the tumor cells. TILT-123 is designed to replicate only in cells with defects in the p16/Rb/E2F pathway, attributed to a mutation common in many solid tumors. Replacement of the Ad5 capsid protein knob with a knob domain from serotype 3 causes higher transduction in cancer cells as compared to normal cells.

• Tocilizumab - A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. Il-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions.

• Tocladesine - An antimetabolite and a chlorine derivative of the intracellular secondary messenger, cyclic adenosine 3,5-monophosphate (cAMP), with potential antineoplastic activity. Tocladesine appears to be converted to 8-chloro-adenosine by phosphodiesterases and subsequently phosphorylated to 8-chloro-ATP, which functions as a purine analogue and competes with ATP in transcription. In addition, generation of 8-chloro-ATP depletes endogenous ATP pool that is essential for many biological reactions in intracellular energy transfer. As a result, this agent causes RNA synthesis inhibition, blocks cellular proliferation, and induces apoptosis.

• Tocotrienol - Any of the four forms, alpha, beta, gamma and delta, of a member of the vitamin E family, with potential hypocholesterolemic, antithrombotic, antioxidant, immunomodulating and antineoplastic activities. Tocotrienol inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, thereby lowering cholesterol levels. In addition, tocotrienol acts through multiple signal transduction pathways to induce cell cycle arrest and caspase-mediated apoptosis, and to decrease tumor cell proliferation. In addition, this agent may inhibit angiogenesis through the blockage of vascular endothelial growth factor receptor (VEGFR) and the subsequent inhibition of tumor cell-induced vessel formation. Also, this agent prevents free radical formation and inhibits lipid peroxidation, thereby preventing DNA cell damage. Tocotrienol farnesyl isoprenoid side chains contain 3 double bonds, which are absent in tocopherols, likely contribute to its anti-cancer activities.

• Tocotrienol-rich fraction - An orally available nutritional supplement containing high amounts of the vitamin E family member tocotrienol with antioxidant, hypolipidemic and potential immunomodulating and antiproliferative activity. Upon oral administration, tocotrienol-rich fraction (TRF) accumulates in tumor cells and induces cell cycle arrest, programmed cell death, and inhibits tumor cell proliferation. In addition, this agent suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and inhibits angiogenesis. Rice bran oil, palm oil and annatto seed oil are common sources of TRF.

• Tolebrutinib - An orally bioavailable, brain-penetrant, selective, small molecule inhibitor of Bruton's tyrosine kinase (BTK), with potential immunomodulatory and anti-inflammatory activities. Upon oral administration, tolebrutinib is able to cross the blood-brain barrier and inhibits the activity of BTK both peripherally and in the central nervous system (CNS). This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway, and the resulting immune activation and inflammation. The inhibition of BTK activity also prevents microglial inflammatory signaling in the CNS, and the resulting immune activation, neuroinflammation and neurodegeneration. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival. In addition to B cells, BTK is also expressed in innate immune cells, including macrophages and microglia, and plays an important role in the regulation of microglial inflammatory signaling.

• Toll-like receptor 7 agonist dsp-0509 - A synthetic, small molecule, toll-like receptor (TLR) 7 agonist, with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, TLR7 agonist DSP-0509 activates TLR7, resulting in type I interferon secretion and activation of cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune responses. TLR7 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.

• Tolnidamine - An indazole carboxylic acid derivative with antispermatogenic and potential antineoplastic activity. As a male contraceptive, tolnidamine may irreversibly inhibit sperm production. This agent is less nephrotoxic than ionidamide, but it is just as effective in antispermatogenic action to ionidamide.

• Tomaralimab - A humanized immunoglobulin (Ig) G4 monoclonal antibody directed against toll-like receptor type 2 (TLR2), with potential anti-inflammatory and antineoplastic activities. Upon intravenous administration, tomaralimab binds to the ligand-binding site on the TLR2 receptor and blocks the activation of TLR2-mediated innate immunity signaling. This prevents the TLR2-mediated production of pro-inflammatory mediators and prevents inflammation. TLR2, a member of the TLR family primarily found on leukocytes, plays a key role in the activation of innate immunity; it is overexpressed in various inflammatory diseases and in certain types of cancer.

• Tomato-soy juice - A juice containing tomato extract and soy protein with potential chemopreventive and antiproliferative activities. Tomato-soy juice contains phytochemicals, including flavonoids, such as the soy isoflavone genistein, and carotenoids, including lycopene. These phytochemicals may exhibit antioxidative activity, antitumor activity by modulating certain tumor-associated signal transduction pathways, and apoptosis-inducing activity.

• Tomivosertib - An orally bioavailable inhibitor of mitogen-activated protein kinase (MAPK)-interacting serine/threonine-protein kinase 1 (MNK1) and 2 (MNK2), with potential antineoplastic activity. Upon oral administration, tomivosertib binds to and inhibits the activity of MNK1 and 2. This prevents MNK1/2-mediated signaling, and inhibits the phosphorylation of certain regulatory proteins, including eukaryotic translation initiation factor 4E (eIF4E), that regulate the translation of messenger RNAs (mRNAs) involved in tumor cell proliferation, angiogenesis, survival and immune signaling. This inhibits tumor cell proliferation in MNK1/2-overexpressing tumor cells. MNK1/2 are overexpressed in a variety of tumor cell types and promote phosphorylation of eIF4E; eIF4E is overexpressed in many tumor cell types and contributes to tumor development, maintenance and resistance.

• Topical betulinic acid - A topical formulation of a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) with antiinflammatory, anti-HIV and antineoplastic activities. Betulinic acid induces apoptosis through induction of changes in mitochondrial membrane potential, production of reactive oxygen species, and opening of mitochondrial permeability transition pores, resulting in the release of mitochondrial factors involved in apoptosis, activation of caspases, and DNA fragmentation. Although originally thought to exhibit specific cytotoxicity against melanoma cells, this agent has been found to be cytotoxic against non-melanoma tumor cell types including neuroectodermal and brain tumor cells.

• Topical celecoxib - A topical cream formulation containing celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), with anti-inflammatory and potential keratolytic, chemopreventive and antineoplastic activities. Upon topical application to the affected area, celecoxib selectively binds to and inhibits cyclooxygenase-2 activity (COX-2), which may result in localized keratinocyte apoptosis. The breakdown of keratinocytes prevents their proliferation locally and may reduce tumor cell proliferation.

• Topical fluorouracil - : A topical formulation containing the antimetabolite 5-fluorouracil (5-FU), with antineoplastic activity. Upon topical administration, 5-FU is converted into the active metabolite 5-fluoroxyuridine monophosphate (F-UMP), which competes with uracil during RNA synthesis and inhibits RNA processing. Conversion of 5-FU into another active metabolite, 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP), inhibits thymidylate synthase; this results in the depletion of thymidine triphosphate (TTP), one of the four nucleotide triphosphates used in DNA synthesis, and thus inhibits DNA synthesis. Altogether, this prevents the proliferation of tumor cells locally.

• Topical gemcitabine hydrochloride - A topical preparation of gemcitabine hydrochloride with antineoplastic activity. Gemcitabine, an analogue of the antimetabolite nucleoside deoxycytidine, is converted intracellularly to the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis.

• Topical potassium dobesilate - A topical formulation composed of an inhibitor of fibroblast growth factor (FGF), with potential antineoplastic activity. Upon topical administration potassium dobesilate selectively binds to and blocks the activity of FGF, interferes with the binding of FGF to FGFR and prevents FGFR-mediated signaling. This inhibits angiogenesis and tumor cell proliferation, and induces cell death in FGFR-overexpressing tumor cells. FGF plays a key role in angiogenesis, tumor cell proliferation, survival and invasiveness, and is upregulated in many tumor cell types.

• Topical trichloroacetic acid - A topical solution containing the caustic agent trichloroacetic acid (TCA), with potential keratolytic, anti-viral and antineoplastic activities. Upon topical application to the affected area, TCA causes tissue necrosis through coagulation of proteins, leads to the destruction of human papilloma virus (HPV)-associated warts and inhibits HPV-driven proliferation of cancer cells.

• Topixantrone - A 9-aza-anthrapyrazole antineoplastic antibiotic. Topixantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Compared to other DNA intercalators, this agent shows minimal cardiotoxicity.

• Topoisomerase i inhibitor genz-644282 - A non-camptothecin inhibitor of topoisomerase I with potential antineoplastic activity. Topoisomerase I inhibitor Genz-644282 binds to and inhibits the enzyme topoisomerase I, which may result in the inhibition of repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations.

• Topoisomerase i inhibitor lmp400 - An indenoisoquinoline and non-camptothecin inhibitor of topoisomerase I (Top I) with potential antineoplastic activity. Topoisomerase I inhibitor LMP400 binds to the topoisomerase I-DNA covalent cleavage complexes, and inhibits repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. Compared to camptothecins, indenoisoquinolines are chemically stable, produce stable Top I-DNA cleavage complexes, induce unique DNA cleavage sites and appear more resistant to multidrug efflux pumps.

• Topoisomerase i inhibitor lmp776 - An indenoisoquinoline and non-camptothecin inhibitor of topoisomerase I (Top I) with potential antineoplastic activity. Topoisomerase I inhibitor LMP776 binds to the topoisomerase I-DNA covalent cleavage complexes, and inhibits repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. Compared to camptothecins, indenoisoquinolines are chemically stable, produce stable Top I-DNA cleavage complexes, induce unique DNA cleavage sites and appear more resistant to multidrug efflux pumps.

• Topoisomerase i/ii inhibitor nev-801 - A multi-targeted agent with potential antineoplastic activity. Upon administration, NEV-801 appears to selectively inhibit topoisomerase (Topo) I and II, and activates hypoxia-inducible factor 1 (HIF-1) transcription and the expression of vascular endothelial growth factor (VEGF) mRNA. NEV-801 is also able to overcome multidrug resistance (MDR) 1-mediated resistance.

• Topoisomerase-1 inhibitor lmp744 - An indenoisoquinoline derivative and topoisomerase 1 (Top1) inhibitor, with potential antineoplastic activity. Upon administration, LMP744 binds to and stabilizes cleaved DNA-Top1 complexes, which prevents DNA re-ligation, induces stable, irreversible DNA strand breaks, prevents DNA repair, and leads to cell cycle arrest and apoptosis. As tumor cells proliferate at a much higher rate than normal cells, LMP744 specifically targets cancer cells. Top1, a DNA modifying enzyme essential for transcription, replication, and repair of double-strand DNA breaks, is overexpressed in tumor cells.

• Topoisomerase-ii inhibitor racemic xk469 - The racemic form of a synthetic quinoxaline phenoxypropionic acid derivative with antineoplastic properties. XK469R selectively inhibits topoisomerase II by stabilizing the enzyme-DNA intermediates in which topoisomerase subunits are covalently linked to DNA through 5-phosphotyrosyl linkages, thereby interfering with DNA repair and replication, RNA and protein synthesis. This agent possesses unusual solid tumor selectivity and activity against multidrug-resistant cancer cells. XK469R is more water soluble and active than the pure isomers, R(+)XK469 and S(-)XK469. (NCI05)

• Topoisomerase-ii-beta inhibitor racemic xk469 - The R-isomer of a synthetic quinoxaline phenoxypropionic acid derivative with proapoptotic and antiproliferative activities. R(+)XK469 selectively inhibits topoisomerase II-beta, blocks activation of MEK/MAPK signaling kinases, stimulates caspases, and upregulates p53-dependent proteins, including cyclins A and B1, thereby arresting cancer cells in the G2/M phase of the cell cycle. Both R(+) and S(-) isomers of this agent are cytotoxic, although the R-isomer is more potent. (NCI05)

• Topotecan - A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Topotecan inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA covalent complexes during S phase of cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery.

• Topotecan hydrochloride - The hydrochloride salt of a semisynthetic derivative of camptothecin with antineoplastic activity. During the S phase of the cell cycle, topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. Camptothecin is a cytotoxic quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata.

• Topotecan hydrochloride liposomes - The hydrochloride salt of a semisynthetic derivative of camptothecin mixed with sphingomyelin/cholesterol and sonicated to form small unilamellar vesicles containing topotecan, with potential antineoplastic activity. Topotecan hydrochloride liposomes mediates efficient drug delivery of topotecan into the cytosol from the endosome compartment. During the S phase of the cell cycle, topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery.

• Topotecan sustained-release episcleral plaque - An episcleral plaque containing sustained-release (SR) topotecan, a semisynthetic derivative of camptothecin and a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminate, with potential antineoplastic activity. Upon local application of the topotecan SR episcleral plaque to the eye, topotecan is released in a sustained manner and inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA covalent complexes during S phase of cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. The episcleral plaque allows for local delivery of topotecan for the potential treatment of retinoblastoma.

• Topsalysin - A targeted prodrug consisting of a recombinant modified form of the Aeromonas protoxin, proaerolysin (PA), bearing a prostate-specific protease cleavage site, with potential antineoplastic activity. When injected directly into the prostate, topsalysin is hydrolyzed to the active toxin aerolysin by the serine protease prostate specific antigen (PSA), a protein overexpressed by prostate cancers and prostate cells in hyperplastic prostatic tissue. Aerolysin molecules then oligomerize to form ring-like heptamers that are incorporated into the lipid bilayers of cell membranes, forming large membrane channels and resulting in the leakage of cellular contents and lysis of PSA-expressing prostate cells.

• Torc1/2 kinase inhibitor ds-3078a - An orally bioavailable inhibitor of raptor-mTOR protein complex (TORC1) and rictor-mTOR protein complex (TORC2) with potential antineoplastic activity. TORC1/2 inhibitor DS-3078a binds to and inhibits both TORC1 and TORC2, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. TORC1 and 2 are upregulated in some tumors and play an important role in the PI3K/Akt/mTOR signaling pathway, which is frequently dysregulated in human cancers.

• Toremifene - A nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which are manifested according to tissue type or species.

• Toremifene citrate - The citrate salt of a nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which is manifested depending on the tissue or species.

• Toripalimab - A humanized immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (programmed death-1; PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, toripalimab binds to PD-1 and inhibits the binding of PD-1 to its ligands, programmed cell death-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). This prevents the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of both T-cells and T-cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the Ig superfamily that is expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligands; it plays an important role in tumor evasion from host immunity.

• Tosedostat - A proprietary orally bioavailable inhibitor of the M1 family of aminopeptidases with potential antineoplastic activity. Aminopeptidase inhibitor CHR-2797 is converted intracellularly into a poorly membrane-permeable active metabolite (CHR-79888) which inhibits the M1 family of aminopeptidases, particularly puromycin-sensitive aminopeptidase (PuSA), and leukotriene A4 (LTA4) hydrolase; inhibition of these aminopeptidases in tumor cells may result in amino acid deprivation, inhibition of protein synthesis due to a decrease in the intracellular free amino acid pool, an increase in the level of the proapoptotic protein Noxa, and cell death. Noxa is a member of the BH3 (Bcl-2 homology 3)-only subgroup of the proapoptotic Bcl-2 (B-cell CLL/lymphoma 2) protein family.

• Tositumomab - A murine IgG2 monoclonal antibody directed against the CD20 antigen, found on the surface of B-cells. Tositumomab binds to the CD20 surface membrane antigen, resulting in apoptosis, and may stimulate antitumoral cell-mediated and/or antibody-dependent cytotoxicity.

• Total tumor mrna-pulsed tumor-specific ex vivo-expanded autologous lymphocyte transfer cells - A preparation of ex vivo expanded, autologous lymphocyte transfer cells (xALTs) that are loaded with total tumor RNA (TTRNA) derived from autologous tumor cells, with potential immunostimulatory and antineoplastic activities. Upon re-infusion of the TTRNA-loaded ALTs into the patient, these ALTs may elicit a highly specific cytotoxic T-lymphocyte (CTL) response against the tumor-associated antigens (TAAs) encoded by the TTRNA.

• Total tumor rna-loaded dendritic cell vaccine - A cancer vaccine containing autologous dendritic cells (DCs) that are loaded with total tumor RNA (TTRNA) from a specific tumor, with potential immunostimulatory and antineoplastic activities. Upon administration, TTRNA-loaded DC vaccine may elicit a highly specific cytotoxic T-cell (CTL) response against the tumor-associated antigens (TAAs) encoded by the TTRNA.

• Tovetumab - A humanized monoclonal antibody directed against the platelet-derived growth factor receptor (PDGFR) alpha with potential antineoplastic activity. Tovetumab inhibits activation of the cell-surface tyrosine kinase PDGFR alpha subunit and subsequent triggering of mitogenic signaling pathways, including the JAK/STAT, PI3K/Akt, and MAP kinase pathways. PDGFR alpha acts as a mitogenic signaling receptor for cells of mesenchymal origin and inhibition of receptor activity may inhibit tumor cell proliferation.

• Tozasertib lactate - The lactate salt of tozasertib, a synthetic, small-molecule Aurora kinase inhibitor with potential antitumor activity. Tozasertib binds to and inhibits Aurora kinases (AKs), thereby inducing apoptosis in tumor cells in which AKs are overexpressed. AKs, a family of serine-threonine kinases, are essential for mitotic progression, spindle formation, centrosome maturation, chromosomal segregation, and cytokinesis.

• Tp40 immunotoxin - A chimeric fusion protein containing human transforming growth factor alpha (TGF-a) covalently linked to a truncated form of the bacterial toxin Pseudomonas exotoxin A, PE40, with potential antitumor activity. PE40 lacks the cell-binding domain, but retains domains II and III that are involved in membrane translocation and inhibition of protein synthesis in eukaryotic cells. TGF-a moiety of the TP40 immunotoxin binds to and activates epidermal growth factor receptor (EGFR), a tyrosine kinase receptor overexpressed on certain cancer cells. After internalization, the endotoxin moiety of the immunotoxin-receptor complex causes protein synthesis inhibition via modifying translation elongation factor 2 (EF-2), thereby impedes tumor cell growth and proliferation.

• Trabectedin - A tetrahydroisoquinoline alkaloid isolated from the marine tunicate Ecteinascidia turbinata with potential antineoplastic activity. Binding to the minor groove of DNA, trabectedin interferes with the transcription-coupled nucleotide excision repair machinery to induce lethal DNA strand breaks and blocks the cell cycle in the G2 phase.

• Trabedersen - A transforming growth factor (TGF)-beta2 specific phosphorothioate antisense oligodeoxynucleotide with the sequence 5'-CGGCATGTCTATTTTGTA-3', with potential antineoplastic activity. Trebedersen binds to TGF-beta2 mRNA causing inhibition of protein translation, thereby decreasing TGF-beta2 protein levels; decreasing intratumoral TGF-beta2 levels may result in the inhibition of tumor cell growth and migration, and tumor angiogenesis. TGF-beta2, a cytokine often over-expressed in various malignancies, may play an important role in promoting the growth, progression, and migration of tumor cells.

• Trametinib - An orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MEK MAPK/ERK kinase) with potential antineoplastic activity. Trametinib specifically binds to and inhibits MEK 1 and 2, resulting in an inhibition of growth factor-mediated cell signaling and cellular proliferation in various cancers. MEK 1 and 2, dual specificity threonine/tyrosine kinases often upregulated in various cancer cell types, play a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth.

• Trametinib dimethyl sulfoxide -

• Trans sodium crocetinate - The sodium salt of the trans-isomer of the carotenoid crocetin with potential antihypoxic and radiosensitizing activities. Trans sodium crocetinate (TSC) increases the diffusion rate of oxygen in aqueous solutions such as from plasma to body tissue. The agent has been shown to increase available oxygen during hypoxic and ischemic conditions that may occur in hemorrhage, vascular and neurological disorders, and in the tumor microenvionment.

• Transdermal 17beta-estradiol gel bhr-200 - A proprietary, transdermal, hydroalcoholic gel formulation containing 17beta-estradiol, with potential antineoplastic activity. Upon topical administration, 17beta-estradiol exerts its antineoplastic effect(s) through as of yet not fully elucidated mechanism(s) of action(s). This formulation may induce feedback inhibition via the hypothalamic-pituitary-gonadal axis feedback loop, block the secretion of luteinizing hormone (LH) and prevent the release of testosterone from Leydig cells in the testes, thus suppressing testosterone secretion. In addition, 17beta-estradiol inhibits enzymes involved in steroidogenesis, thereby further inhibiting androgen production. Since testosterone is required to sustain prostate growth, reducing testosterone levels may inhibit hormone-dependent prostate cancer cell proliferation. In addition, 17beta-estradiol prevents bone loss, and suppresses andropause symptoms, such as hot flashes, which appear during androgen-deprivation therapy (ADT) where the standard of care is the use of gonadotrophin releasing hormone (GnRH) analogs. Compared to oral estrogens, the topical gel formulation lowers the risk of cardiovascular side effects.

• Transdermal 4-hydroxytestosterone - A transdermal formulation containing 4-hydroxytestosterone (4-OHT), a steroidal aromatase inhibitor (AI) and androgen receptor (AR) antagonist, with potential antineoplastic activity. 4-OHT is largely converted into 4-hydroxyandrostenedione (4-OHA) and irreversibly binds to and inhibits aromatase, thereby blocking the conversion of androstenedione to estrone, and testosterone to estradiol. This may inhibit tumor cell proliferation in estrogen-dependent tumor cells. In addition, 4-OHT binds to the AR and may inhibit AR-mediated tumor cell growth. Aromatase, a cytochrome P-450 enzyme, is overexpressed in a variety of cancer cells; it plays a key role in estrogen biosynthesis. Compared to oral 4-OHT, the transdermal formulation allows for continuous release of 4-OHT into the bloodstream and prevents first pass metabolism by the liver.

• Transferrin receptor-targeted anti-rrm2 sirna calaa-01 - A proprietary transferrin receptor-targeted nanoparticle preparation of a non-chemically modified small-interfering RNA (siRNA) directed against the M2 subunit of ribonucleotide reductase (RRM2) with potential antineoplastic activity. Upon administration, transferrin receptor-targeted anti-RRM2 siRNA CALAA-01 binds to transferrin receptors (TfRs), releasing anti-RRM2 siRNA after endocytosis; anti-RRM2 siRNA silences the expression of RRM2 via the RNAi pathway, impeding the assembly of the holoenzyme ribonucleotide reductase (RR) which catalyzes the production of deoxyribonucleotides. As a result, inhibition of cellular proliferation may occur in cells expressing TfR, a cell surface protein overexpressed on various cancer cell types.

• Transferrin receptor-targeted liposomal p53 cdna - A cationic liposomal, tumor-targeting p53 (TP53) gene delivery system with potential anti-tumor activity. Transferrin receptor-targeted liposomal p53 cDNA contains plasmid DNA encoding the tumor suppressor protein p53 packaged in membrane-like liposome capsules that are complexed with anti-transferrin receptor single-chain antibody (TfRscFv). Upon systemic administration, the anti-TfRscFv selectively binds to tumor cells expressing transferrin receptors. The p53 plasmid is delivered into the nucleus and as a result, p53 protein is produced in tumor cells that have altered p53 function. This results in the restoration of normal cell growth control mechanisms as well as normal response mechanisms to DNA damage.

• Transferrin-crm107 - A synthetic targeted protein toxin which consists of human transferrin (Tf) conjugated to a diphtheria toxin that contains a point mutation (CRM107). After binding to the transferrin receptor expressed on the tumor cell surface, transferrin-CRM107 is internalized, where the diphtheria toxin moiety exerts its cytotoxic effect intracellularly by inhibiting protein synthesis through ADP-ribosylation of elongation factor.

• Transgenic lymphocyte immunization vaccine - A vaccine consisting of a preparation of allogeneic lymphocytes that encode a gene for telomerase. In transgenic lymphocyte immunization, the transgenic cells are infused into the patient, where they serve as antigen- presenting cells (APCs) with the dual function of antigen synthesis and presentation. Vaccination produces an immune response targeting cancer cells expressing telomerase.

• Tranylcypromine sulfate - The sulfate salt form of tranylcypromine, an orally bioavailable, nonselective, irreversible, non-hydrazine inhibitor of both monoamine oxidase (MAO) and lysine-specific demethylase 1 (LSD1/BHC110), with antidepressant and anxiolytic activities, and potential antineoplastic activities. Upon oral administration, tranylcypromine exerts its antidepressant and anxiolytic effects through the inhibition of MAO, an enzyme that catalyzes the breakdown of the monoamine neurotransmitters serotonin, norepinephrine, epinephrine and dopamine. This increases the concentrations and activity of these neurotransmitters. Tranylcypromine exerts its antineoplastic effect through the inhibition of LSD1. Inhibition of LSD1 prevents the transcription of LSD1 target genes. LSD1, a flavin-dependent monoamine oxidoreductase and a histone demethylase, is upregulated in a variety of cancers and plays a key role in tumor cell proliferation, migration, and invasion.

• Trapoxin - An epoxide-containing cyclotetrapeptide with antitumor activity. It is an irreversible inhibitor of histone deacetylase.

• Trastuzumab - A recombinant humanized monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). After binding to HER2 on the tumor cell surface, trastuzumab induces an antibody-dependent cell-mediated cytotoxicity against tumor cells that overexpress HER2. HER2 is overexpressed by many adenocarcinomas, particularly breast adenocarcinomas.

• Trastuzumab conjugate bi-con-02 - A conjugated form of trastuzumab, a humanized monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2; ERBB2), with potential immunomodulating and antineoplastic activities. Upon administration, the trastuzumab conjugate BI-CON-02 targets and binds to HER2 on the tumor cell surface, thereby inducing both cytotoxic T-lymphocyte (CTL) and antibody-dependent cell-mediated cytotoxicity (ADCC) responses against tumor cells that overexpress HER2. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.

• Trastuzumab deruxtecan - An antibody-drug conjugate (ADC) composed of trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to deruxtecan, a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with antineoplastic activity. Upon administration of trastuzumab deruxtecan, trastuzumab targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, deruxtecan binds to and inhibits Top1-DNA complexes, which results in an inhibition of DNA replication, cell cycle arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. In addition, trastuzumab deruxtecan induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect.

• Trastuzumab duocarmazine - An antibody-drug conjugate (ADC) composed of the recombinant humanized anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab linked, via a cleavable linker, to the duocarmycin prodrug, seco-duocarmycin-hydroxybenzamide-azaindole (seco-DUBA), with potential antineoplastic activity. Upon administration of trastuzumab duocarmazine, the trastuzumab moiety binds to HER2 on the tumor cell surface, which triggers the endocytosis of this agent. The linker is then cleaved inside the tumor cell by proteases at the dipeptide valine-citrulline (vc), and releases the active moiety, duocarmycin. Duocarmycin binds to the minor groove of DNA, alkylates adenine at the N3 position, and induces cell death. In addition, trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells that overexpress HER2. HER2 is overexpressed by many carcinomas and is associated with a poor prognosis.

• Trastuzumab emtansine - An antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1 via a nonreducible thioether linkage (MCC) with potential antineoplastic activity. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surfaces; upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers.

• Trastuzumab monomethyl auristatin f - An antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the auristatin analog and potent microtubule inhibitor monomethyl auristatin F (MMAF), with potential antineoplastic activity. Upon administration of trastuzumab monomethyl auristatin F, the trastuzumab moiety binds to HER2 on tumor cell surfaces; upon internalization, the MMAF moiety binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.

• Trastuzumab/tesirine antibody-drug conjugate adct-502 - An antibody-drug conjugate (ADC) consisting of an engineered version of the humanized monoclonal anti-human epidermal growth factor receptor 2 (HER2) immunoglobulin G1 (IgG1) trastuzumab that is site-specifically conjugated, via a cleavable linker, to the cytotoxic, DNA cross-linking pyrrolobenzodiazepine (PBD) dimer-based drug tesirine, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the trastuzumab moiety of trastuzumab/tesirine ADC ADCT-502 targets the cell surface antigen HER2, which is expressed on various cancer cells. Upon antibody/antigen binding, internalization of the ADC and cleavage of the linker, the cytotoxic PBD moiety is released. The imine groups of tesirine bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death and inhibits the proliferation of HER2-overexpressing tumor cells. The tumor-associated antigen (TAA) HER2 is expressed by various solid tumors and is associated with a poor prognosis.

• Trastuzumab-tlr 7/8 agonist bdc-1001 - An immune stimulating antibody conjugate (ISAC) consisting of trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, conjugated to a Toll-like receptor (TLR) 7/8 dual agonist, with potential immunostimulating and antineoplastic activities. Upon administration of trastuzumab-TLR 7/8 agonist BDC-1001, the trastuzumab moiety targets and binds to HER2 expressed on tumor cells and, simultaneously, the TLR 7/8 dual agonist moiety targets, binds to and activates TLR7/8 expressed on antigen-presenting cells (APCs), specifically dendritic cells (DCs), in the tumor microenvironment (TME). The trastuzumab binding to the tumor cells causes the engulfment of the BDC-1001-bound tumor cells by tumor-associated myeloid (TAM) cells and the TAMs travel to the lymph nodes. The DCs activated by the TLR7/8 agonist causes the activation of TLR7/8-mediated pathways, and stimulates the maturation and activation of DCs, thereby re-activating the immune system against the tumor cells. Activation of DCs results in the production of pro-inflammatory cytokines, and the activation of cytotoxic T-lymphocyte (CTL)- and B-lymphocyte-mediated immune responses against tumor-associated antigens (TAAs), which lead to tumor cell lysis. TLR7 and 8, members of the TLR family, play fundamental roles in the activation of the innate immune system, myeloid cell responses and tumor antigen presentation. HER2 is overexpressed by a variety of tumor cell types.

• Trebananib - An angiopoietin (Ang) 1 and 2 neutralizing peptibody, with potential antiangiogenic activity. AMG 386 targets and binds to Ang1 and Ang2, thereby preventing the interaction of the angiopoietins with their target tie2 receptors. This may inhibit angiogenesis and may eventually lead to an inhibition of tumor cell proliferation.

• Tremelimumab - A human IgG2 monoclonal antibody directed against the T-cell receptor protein cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Tremelimumab binds to CTLA4 and blocks the binding of the antigen-presenting cell ligands B7-1 and B7-2 to CTLA4, resulting in inhibition of B7-CTLA4-mediated downregulation of T-cell activation; subsequently, B7-1 or B7-2 may interact with another T-cell surface receptor protein, CD28, resulting in a B7-CD28-mediated T-cell activation unopposed by B7-CTLA4-mediated inhibition.

• Treosulfan - The prodrug of a bifunctional sulfonate alkylating agent with myeloablative, immunosuppressive, and antineoplastic activities. Under physiological conditions, treosulfan converts nonenzymatically to L-diepoxybutane via a monoepoxide intermediate. The monoepoxide intermediate and L-diepoxybutane alkylate DNA at guanine residues and produce DNA interstrand crosslinks, resulting in DNA fragmentation and apoptosis. In escalated doses, this agent also exhibits myeloablative and immunosuppressive activities.

• Tretazicar - A prodrug of a bifunctional alkylating, dinitrobenzamide derivative with antineoplastic activity. Tretazicar can be activated by the human enzyme quinone oxidoreductase 2 (NQO2) in the presence of the cosubstrate caricotamide, an analogue of the natural cosubstrate dihydronicotinamide riboside (NRH), which acts as an electron donor. The resulting active, but short-lived metabolite, dinitrobenzamide, leads to DNA replication inhibition and the induction of apoptosis in NQO2 expressing cancer cells. Due to the lack of the natural cosubstrate NRH, NQO2 expression is normally latent but is upregulated in certain types of tumor cells.

• Tretinoin - A naturally-occurring acid of retinol. Tretinoin binds to and activates retinoic acid receptors (RARs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, and inhibition of tumorigenesis. This agent also inhibits telomerase, resulting in telomere shortening and eventual apoptosis of some tumor cell types. The oral form of tretinoin has teratogenic and embryotoxic properties.

• Tretinoin liposome - An intravenous formulation of tretinoin (vitamin A acid or all-trans retinoic acid) encased in liposomes. Tretinoin is a naturally occurring retinoic acid agent that binds to and activates retinoic acid receptors (RAR), effecting changes in gene expression that lead to cell differentiation, decreased cell proliferation, and inhibition of carcinogenesis. This agent also inhibits telomerase, leading to telomere shortening and eventual apoptosis of certain tumor cell types. Liposome encapsulation extends the half-life of intravenously administered tretinoin.

• Triapine - A synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity. Triapine inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. This agent has been shown to inhibit tumor growth in vitro.

• Triazene derivative cb10-277 - A synthetic derivative of dimethylphenyl-triazene related to dacarbazine, with antineoplastic properties. Related to the agent dacarbazine, CB10-277 is converted in vivo to a monomethyl triazene form that alkylates DNA, resulting in inhibition of DNA replication and repair; in addition, this agent may act as a purine analogue, resulting in inhibition of DNA synthesis, and may interact with protein sulfhydryl groups.

• Triazene derivative trin2755 - A synthetic triazene derivative with antineoplastic activity. Upon metabolic activation via N-demethylation, TriN2755 is converted into highly reactive carbocations that can alkylate DNA and other macromolecules, thereby resulting in DNA cross links, inhibiting DNA replication and repair, and subsequently inducing apoptosis. This agent has high hydrophilicity and photostability and shows a favorable toxicity profile over the other triazenes.

• Triazinate - A synthetic dihydrotriazine derivative with antineoplastic properties. As an antifolate agent related to methotrexate (MTX), triazinate inhibits the enzyme dihydrofolate reductase (DHFR), resulting in decreased tetrahydrofolate production and interference with thymidylate synthesis. Unlike MTX, this agent is not converted to polyglutamate forms. Triazinate also inhibits the transport of folates and may be selectively toxic to MTX-resistant tumor cells.

• Triaziquone - An aziridinylbenzoquinone-based alkylating agent with potential antineoplastic activity. The alkylating group in triaziquone becomes activated upon reduction of quinone to the hydroquinone form. This eventually results in the alkylation and crosslinking of DNA, thereby inhibiting DNA replication followed by an induction of apoptosis. In addition, reactive oxygen species may form during redox cycling which may contribute to this agent's cytotoxic activity.

• Tributyrin - A triglyceride prodrug of butyric acid with potential antineoplastic activity. Butyrate, the active metabolite of tributyrin, inhibits histone deacetylase, resulting in increased differentiation, decreased proliferation, cell cycle arrest, and apoptosis in some tumor cell lines.

• Triciribine phosphate - The phosphate salt of the synthetic, cell-permeable tricyclic nucleoside triciribine with potential antineoplastic activity. Triciribine inhibits the phosphorylation, activation, and signalling of Akt-1, -2, and -3, which may result in the inhibition of Akt-expressing tumor cell proliferation. Akts are anti-apoptotic serine/threonine-specific protein kinases that phosphorylate and inactivate components of the apoptotic machinery, including Bcl-xL/Bcl-2-associated death promoter (BAD) and caspase 9.

• Trientine hydrochloride - The hydrochloride salt form of a metal chelating agent with potential anti-angiogenic activity. Trientine chelates excess copper (Cu) ions in the body; the excess copper is subsequently removed from the body through the kidneys. As Cu is an essential cofactor for cuproenzymes, such as superoxide dismutase 1 (SOD1), depletion of copper may inhibit the activation of signal transduction pathways required for cellular proliferation and angiogenesis. In addition, trientine may inhibit copper-induced secretion of interleukin-8 (IL-8).

• Triethylenemelamine - A trisaziridine alkylating agent with antineoplastic and carcinogenic properties. Used to induce cancer in experimental animal models, triethylenemelamine ethylates DNA, resulting in inhibition of DNA replication, unscheduled DNA synthesis, chromosomal aberrations, and sister chromatid exchanges. This agent also exhibits reproductive toxicities.

• Trifluridine - A fluorinated thymidine analog with potential antineoplastic activity. Trifluridine is incorporated into DNA and inhibits thymidylate synthase, resulting in inhibition of DNA synthesis, inhibition of protein synthesis, and apoptosis. This agent also exhibits antiviral activity.

• Trifluridine and tipiracil hydrochloride - An orally bioavailable combination agent composed of the cytotoxic pyrimidine analog trifluridine (5-trifluoro-2'-deoxythymidine or TFT) and a thymidine phosphorylase inhibitor (TPI) tipiracil hydrochloride, in a molar ratio of 1.0:0.5 (TFT:TPI), with potential antineoplastic activity. After oral administration of TAS-102, TFT is phosphorylated to the active monophosphate form TF-TMP, which binds covalently to the active site of thymidylate synthase, thereby reducing the nucleotide pool levels required for DNA replication. Furthermore, the triphosphate form TF-TTP can be incorporated into DNA, which induces DNA fragmentation and leads to the inhibition of tumor growth. TPI exhibits a dual effect: 1) an anti-angiogenic effect mediated through the inhibition of thymidine phosphorylase, which plays important role in nucleotide metabolism and a variety of development processes, including angiogenesis, 2) increased bioavailability of the normally short-lived antimetabolite TFT by preventing its degradation into the inactive form trifluorothymine (TF-Thy). The synergistic effect of the components in TAS-10 may demonstrate antitumor activity in 5-FU-resistant cancer cells.

• Trilaciclib - A small molecule, competitive inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), with potential antineoplastic and chemoprotective activities. Upon intravenous administration, trilaciclib binds to and inhibits the activity of CDK4/6, thereby blocking the phosphorylation of the retinoblastoma protein (Rb) in early G1. This prevents G1/S phase transition, causes cell cycle arrest in the G1 phase, induces apoptosis, and inhibits the proliferation of CDK4/6-overexpressing tumor cells. In patients with CDK4/6-independent tumor cells, G1T28 may protect against multi-lineage chemotherapy-induced myelosuppression (CIM) by transiently and reversibly inducing G1 cell cycle arrest in hematopoietic stem and progenitor cells (HSPCs) and preventing transition to the S phase. This protects all hematopoietic lineages, including red blood cells, platelets, neutrophils and lymphocytes, from the DNA-damaging effects of certain chemotherapeutics and preserves the function of the bone marrow and the immune system. CDKs are serine/threonine kinases involved in the regulation of the cell cycle and may be overexpressed in certain cancer cell types. HSPCs are dependent upon CDK4/6 for proliferation.

• Trimelamol - A synthetic derivative of trimethylmelamine with antineoplastic properties. An analogue of siderophores (microbial iron chelators), trimelamol induces the formation of a reactive iminium species which may crosslink DNA.

• Trimeric gitrl-fc omp-336b11 - A Fc-engineered human fusion protein composed of two trimers of tumor necrosis factor (ligand) superfamily, member 18 (TNFSF18; GlTRL) linked to an immunoglobulin Fc domain (GITRL-Fc), with potential immunostimulatory and antineoplastic activities. Upon administration, trimeric GITRL-Fc OMP-336B11 targets, binds to and activates its co-stimulatory surface receptor (glucocorticoid-induced tumor necrosis factor receptor (GITR; TNFRSF18) expressed on T-lymphocytes and certain tumor cell types. This activates T-lymphocytes, causes T-lymphocyte proliferation and suppresses the activity of regulatory T-cells (Treg). This promotes cytotoxic T-lymphocyte (CTL)-mediated killing of tumor cells. GITRL, a member of the tumor necrosis factor (TNF) family of ligands, functions to activate the co-stimulatory receptor GITR to enhance T-cell modulated immune responses.

• Trimethylcolchicinic acid - A colchicine analog with potential antineoplastic activity. Trimethylcolchicinic acid binds to tubulin, inhibiting its polymerization into microtubules and preventing cell division.

• Trimetrexate - A methotrexate derivative with potential antineoplastic activity. Trimetrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, with subsequent inhibition of DNA and RNA synthesis. Trimetrexate also exhibits antiviral activity.

• Trimetrexate glucuronate - A lipid soluble methotrexate derivative with potential antineoplastic activity. Trimetrexate glucuronate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, with subsequent inhibition of DNA and RNA synthesis. Trimetrexate glucuronate also exhibits antiviral activity.

• Trioxifene - A nonsteroidal selective estrogen receptor modulator (SERM) with potential antineoplastic activity. Trioxifene competes with estradiol in binding to estrogen receptor alpha (ER alpha), thereby inhibiting ER alpha-mediated signal transduction and gene expression. In addition, trioxifene exerts intrinsic estrogenic activity depending on the tissue. Clinical development of trioxifene has not been preceded due to its side effect profile and lack of increased efficacy over tamoxifen.

• Triplatin tetranitrate - A cationic tri-nuclear platinum complex related to cisplatin. BBR 3464 binds to and forms DNA crosslinks and platinum-DNA adducts, preventing DNA replication and tumor cell division.

• Triptolide analog - A water soluble analog of the diterpenoid triepoxide triptolide isolated from the Chinese herb Tripterygium wilfordii Hook.f., with potential antineoplastic activity. Upon intravenous administration, the triptolide analog inhibits heat shock protein 70 (HSP70) and prevents HSP70-mediated inhibition of apoptosis. This leads to both the induction of apoptosis and a reduction of cancer cell growth. HSP70, a molecular chaperone upregulated in various cancer cells, plays a key role in the inhibition of caspase-dependent and -independent apoptosis.

• Triptorelin - A synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion. After chronic, continuous administration, this agent effects sustained decreases in LH and FSH production and testicular and ovarian steroidogenesis. Serum testosterone concentrations may fall to levels typically observed in surgically castrated men.

• Triptorelin pamoate - The pamoate salt of triptorelin, a synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion after prolonged administration. After chronic, continuous administration, a sustained decrease in LH, FSH and testicular and ovarian steroidogenesis is observed. The serum testosterone concentration may fall to levels typically seen in surgically castrated men.

• Tris-acryl gelatin microspheres - An embolic particle composed of water-soluble, compressible, nonabsorbable microspheres composed of tris-acryl gelatin, with potential use for embolization. Upon administration, the tris-acryl gelatin microspheres (TAGM) serve as an embolic agent before surgery for highly vascularized areas, such as those seen in certain tumors, by penetrating into the blood vessel system and blocking blood flow. These microspheres may be used to encapsulate various therapeutic agents; drug-loaded microspheres can then be used as drug delivery vehicles during embolization of tumor vasculature.

• Tritylcysteine - A derivative of cysteine with antimitotic activity and potential antineoplastic activity.

• Tri-virus/gd2-specific allogeneic cytotoxic t-lymphocytes - Allogeneic tri-viral specific, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus (Ad), cytotoxic T-lymphocytes (tV-CTLs) expressing a chimeric antigen receptor (CAR) specific for disialoganglioside GD2 with potential antineoplastic activity. Tri-virus/GD2-specific allogeneic CTLs are produced by transducing tV-CTLs with a GD2-specific CAR retroviral vector. Upon administration, after an allogeneic hematopoietic stem cell transplant, these CTLs may be selective towards EBV, CMV, and Ad-infected cells and GD2-expressing tumor cells. The human glycosphingolipid GD2 is a tumor associated antigen overexpressed on the surface of all tumors of neuroectodermal origin.

• Trk inhibitor azd6918 - An orally available liquid suspension containing the tropomyosin receptor kinase (Trk) inhibitor AZD6918 with potential antineoplastic activity. AZD6918 binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, and may eventually result in cell cycle arrest and apoptosis of tumor cells that express Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.

• Trk inhibitor tqb3558 - An orally available inhibitor of tropomyosin receptor kinase (Trk), with potential antineoplastic activity. Upon oral administration, Trk inhibitor TQB3558 targets and binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation. This may lead to apoptosis of Trk-expressing tumor cells and the inhibition of tumor cell proliferation in Trk-expressing tumors. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.

• Trka inhibitor vmd-928 - An orally bioavailable, selective inhibitor of tropomyosin receptor kinase A (TrkA; neurotrophic tyrosine receptor kinase (NTRK) type 1; NTRK1; TRK1-transforming tyrosine kinase protein), with potential antineoplastic activity. Upon oral administration, VMD-928 specifically targets and binds to TrkA, inhibits neurotrophin-TrkA interaction and prevents TrkA activation. This prevents the activation of downstream signaling pathways and inhibits cell growth in tumors that overexpress TrkA. Uncontrolled TrkA signaling plays an important role in tumor cell growth, survival, invasion and treatment resistance.

• Trodusquemine - A naturally-occurring cholestane and non-competitive, allosteric inhibitor of protein tyrosine phosphatase 1B (PTP1B), with potential hypoglycemic, anti-diabetic, anti-obesity, and antineoplastic activities. Upon administration, trodusquemine selectively targets and inhibits PTP1B, thereby preventing PTP1B-mediated signaling. This prevents the dephosphorylation of the insulin receptor, which improves insulin signaling and insulin sensitivity, and decreases blood glucose levels. In susceptible cancer cells, inhibition of PTP1B causes a reduction of tumor cell proliferation. In addition, as trodusquemine can cross the blood-brain barrier (BBB), it centrally suppresses appetite and causes weight loss. PTP1B, a tyrosine phosphatase, is elevated in certain cancer cells; it is specifically upregulated in human epidermal growth factor receptor 2 (HER2)-driven cancers where it promotes cell growth, and is correlated with a poor prognosis and increased metastatic potential. In diabetes, PTP1B upregulation plays a major role in insulin resistance.

• Trofosfamide - An orally bioavailable oxazaphosphorine prodrug with antineoplastic activity. Trofosfamide (TFF) is metabolized predominantly to the cyclophosphamide analogue ifosfamide (IFO), which is then metabolized by liver cytochrome P450s to the active isophosphoramide mustard (IPM). IPM alkylates DNA to form DNA-DNA cross-links, which may result in inhibition of DNA, RNA and protein synthesis, and ultimately lead to tumor cell apoptosis.

• Troglitazone - An orally-active thiazolidinedione with antidiabetic and hepatotoxic properties and potential antineoplastic activity. Troglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation.

• Tropomyosin receptor kinase inhibitor azd7451 - A tropomyosin receptor kinase (TRK) inhibitor with potential antineoplastic activity. AZD7451 binds to TRK, thereby preventing the neurotrophin-TRK interaction and subsequent TRK activation. This may eventually result in an inhibition of tumor cell proliferation in TRK-expressing tumor cells. TRK, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth, invasion and survival.

• Troriluzole - A formulation comprised of a prodrug form of the benzothiazole derivative riluzole, with potential anti-depressant, anxiolytic and antineoplastic activities. Following oral administration, troriluzole is converted into the active form riluzole. While the mechanism of action of riluzole is unknown, its pharmacological activities, some of which may be related to its effect, include the following: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. These activities may result in myorelaxation and sedation due to the blockade of glutamatergic neurotransmission. Additionally, these activities may result in the inhibition of enzymes that are necessary for cell growth, which may decrease tumor cell growth and metastasis.

• Troxacitabine - A dioxolane derivative and a novel L-configuration deoxycytidine analogue with potent antineoplastic activity. When incorporated into growing chain during DNA replication, troxacitabine stops DNA polymerization due to its unnatural L-configuration, in contrast to the normal nucleotides with D-configuration. As a result, this agent terminates DNA synthesis upon incorporated into DNA molecules, and consequently interrupts tumor cell proliferation.

• Troxacitabine nucleotide prodrug miv-818 - A liver-targeting nucleotide phosphoramidate prodrug of troxacitabine monophosphate (TRX-MP), a dioxolane derivative and L-configuration deoxycytidine analogue, with potential antineoplastic activity. Upon oral administration, MIV-818 is rapidly and specifically hydrolyzed in hepatocytes by liver carboxylesterase 1 (carboxylesterase 1, CE-1), generating high levels of the chain-terminating nucleotide, troxacitabine triphosphate (TRX-TP) in the liver. TRX-TP is then incorporated into tumor cell DNA, leading to termination of DNA synthesis and inhibition of tumor cell proliferation.

• Trp2 mrna-electroporated autologous langerhans-type dendritic cell vaccine - A cancer cell vaccine composed of autologous human Langerhans-type dendritic cells (also known as Langerhans cells or LCs) that are electroporated with mRNA encoding full-length murine tyrosinase-related peptide 2 (TRP2), with potential antineoplastic and immunomodulating activities. Upon vaccination, the TRP2 mRNA-electroporated autologous Langerhans-type dendritic cell vaccine may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against TRP2-expressing tumor cells. TRP2, a tautomerase involved in the synthesis of melanin, is only expressed in melanomas, melanocytes, and the retina. The LCs are differentiated from CD34 positive hematopoietic progenitor cells.

• Trpm8 agonist d-3263 - A small-molecule agonist for transient receptor potential melastatin member 8 (TRPM8 or Trp-p8), with potential antineoplastic activity. Upon administration, TRPM8 agonist D-3263 targets, binds to and activates TRPM8, which may result in an increase in intracellular calcium and sodium influx; the disruption of calcium and sodium homeostasis; and the induction of cell death in TRPM8-expressing tumor cells. This agent may decrease dihydrotestosterone (DHT) levels, which may contribute to its inhibitory effects on prostate cancer and benign prostatic hyperplasia (BPH). TRPM8 is a transmembrane calcium channel protein that is normally expressed in prostate cells and appears to be overexpressed in BPH and in prostate cancer.

• Trpv6 calcium channel inhibitor sor-c13 - An inhibitor of transient receptor potential cation channel vanilloid family member 6 (TRPV6, CaT1 or CATL) with potential antineoplastic activity. TRPV6 calcium channel inhibitor SOR-C13 binds to TRPV6 and prevents the influx of calcium ions into TRPV6-expressing tumor cells. This inhibits the activation of nuclear factor of activated T-cell (NFAT) transcription complex which may result in an inhibition of calcium-dependent cancer cell proliferation and an induction of apoptosis in tumor cells overexpressing TRPV6. The TRPV6 ion channel plays a key role in calcium homeostasis and is highly selective for calcium compared to other cations; it is overexpressed in a variety of tumors and initiates tumor cell growth, proliferation and metastases.

• Tsp-1 mimetic abt-510 - A synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8).

• Tsp-1 mimetic fusion protein cvx-045 - A fusion protein containing two thrombospondin (TSP-1)-derived nonamer peptides covalently attached, via a proprietary diketone linker, to a proprietary humanized catalytic monoclonal aldolase monoclonal antibody with potential antiangiogenic and antineoplastic activities. The TSP-1 mimetic peptide moieties of TSP-1 mimetic fusion protein CVX-045 bind to TSP-1 receptors, such as CD36, and inhibit tumor angiogenesis, which may result in the inhibition of tumor cell proliferation. The proprietary humanized catalytic monoclonal aldolase monoclonal antibody contains reactive lysine residues in its binding sites, which react covalently with compounds having a diketone function; the TSP-1 mimetic peptide moieties are then covalently attached to the diketone linkers via a proprietary spacer.

• Tubercidin - An antibiotic and adenosine analog isolated from the bacterium Streptomyces tubercidicus with potential antineoplastic activity. Tubercidin is incorporated into DNA and inhibits polymerases, thereby inhibiting DNA replication and RNA and protein synthesis. This agent also exhibits antifungal and antiviral activities.

• Tubulin binding agent tti-237 - A small synthetic molecule of triazolopyrimidine derivative with potential antitumor activity. With a novel mechanism of action distinct from the action of other vinca alkaloid compounds, TTI-237 specifically binds to tubulin at the vinca site, and promotes the polymerization of tubulin into microtubules. TTI-237 stabilizes tubulin and inhibits microtubule disassembly. This results in cell cycle arrest at the G2/M phase, and leading to cell death.

• Tubulin inhibitor alb 109564 dihydrochloride - A semi-synthetic derivative of the vinka alkaloid vinblastine with potential antineoplastic activity. Tubulin inhibitor ALB 109564 dihydrochloride binds to tubulin monomers and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the G2/M phase of the cell cycle.

• Tubulin inhibitor alb-109564 - A semi-synthetic derivative of the vinka alkaloid vinblastine with potential antineoplastic activity. Tubulin inhibitor ALB-109564 binds to tubulin monomers and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the G2/M phase of the cell cycle. Check for active clinical trials using this agent.

• Tubulin polymerization inhibitor aezs 112 - An orally bioavailable small molecule tubulin polymerization inhibitor with potential antineoplastic activity. Upon oral administration, tubulin polymerization inhibitor AEZS 112 binds to tubulin and prevents its polymerization in tumor blood vessel endothelial cells and tumor cells. This blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent disrupts the tumor vasculature and tumor blood flow, deprives tumor cells of nutrients and induces tumor cell apoptosis. In addition, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization.

• Tubulin polymerization inhibitor veru-111 - An orally available, selective anti-tubulin agent with potential antineoplastic activity. Upon administration, VERU-111 crosslinks alpha- and beta-tubulin subunits, thereby inhibiting microtubule polymerization. This blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent disrupts the tumor vasculature, tumor blood flow, deprives tumor cells of nutrients, and induces apoptosis. VERU-111 is not a substrate of P-glycoprotein (Pgp), an efflux pump that when overexpressed, may confer resistance to taxane therap

• Tubulin-binding agent ssr97225 - An antimitotic tubulin-binding agent with potential antineoplastic activity. Tubulin-binding agent SSR97225 binds to tubulin, arresting the cell cycle at the G2/M checkpoint and preventing mitosis.

• Tucatinib - An orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. Tucatinib selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation.

• Tucidinostat - An orally bioavailable benzamide-type inhibitor of histone deacetylase (HDAC) isoenzymes 1, 2, 3 and 10, with potential antineoplastic activity. Upon administration, tucidinostat binds to and inhibits HDACs, leading to an increase of acetylation levels of histone proteins. This agent also inhibits the expression of kinases in the PI3K/Akt and MAPK/Ras signaling pathways and may result in cell cycle arrest and the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, a class of enzymes that deacetylate chromatin histone proteins, are upregulated in many tumor types and play key roles in gene expression. Compared to some other benzamide-type HDAC inhibitors, chidamide is more stable, more resistant to degradation and has a longer half-life.

• Tucotuzumab celmoleukin - A recombinant fusion protein comprised of a human monoclonal antibody directed against the epithelial cell adhesion molecule (EpCAM or KS) linked to an active interleukin-2 (IL2) molecule with potential antineoplastic activity. Tucotuzumab Celmoleukin recognizes and binds to EpCAM, a cell surface epithelial protein that is expressed on a wide variety of cancer cells, thereby concentrating IL2 in EpCAM-expressing tumor tissue. Subsequently, the localized IL2 moiety of the fusion protein may stimulate a cytotoxic T-cell antitumor immune response.

• Tumor cell vaccine plus bcg - A mixture of allogeneic or autologous tumor cells and bacillus Calmette-Guerin (BCG) in a liquid vehicle with potential antineoplastic activity. Vaccination of the host with tumor cell vaccine plus BCG may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against similar host tumor cells, resulting in decreased tumor growth. The BCG component serves as an adjuvant, a nonspecific stimulator of the immune response.

• Tumor infiltrating lymphocytes-n2-transduced - A preparation of lymphocytes harvested from a patient and genetically modified ex vivo for use in gene therapy for the patient's cancer. Ex vivo, the lymphocytes are transduced with the N2 retroviral vector, which is modified to express a gene whose protein product either kills tumor cells or elicits specific anti-tumor immunity. Genetically modified lymphocytes are infused back into the patient from whom they were harvested, locate to the tumor site, and express the candidate protein that kills tumor cells or stimulates host anti-tumor immunity.

• Tumor peptide-loaded myeloid dendritic cells - A cell-based cancer vaccine composed of myeloid dendritic cells (myDCs) pulsed with tumor peptides with potential immunostimulatory and antineoplastic activities. Upon administration, the tumor peptide-loaded myDCs stimulate a specific cytotoxic T-lymphocyte (CTL) response against the tumor cells, resulting in tumor cell lysis.

• Tumor-cells apoptosis factor hormone-peptide - A synthetic 14-amino acid peptide derived from a novel human peptide hormone, Tumor-Cells Apoptosis Factor (TCApF), with potential antineoplastic activity. Upon intravenous administration, tumor-cells apoptosis factor hormone-peptide binds to the T1/ST2 receptor (IL1RL1) and activates both caspase 8 and Bcl-2 mediated apoptosis, in addition to the activation of p38 MAPK and JNK signaling cascades in tumor cells. Furthermore, this agent inhibits angiogenesis by suppressing the expressions of vascular endothelial growth factor A (VEGFA) and fms-related tyrosine kinase 1 (VEGFR1). Tumor-cells apoptosis factor hormone-peptide also modulates immune system responses via increasing the expressions of interleukin-10 and anti-angiogenic interleukin. T1/ST2 receptor, a member of the toll/interleukin-1 receptor superfamily, is overexpressed in certain cancer cells.

• Type-1 polarized dendritic cell-induced antigen-specific autologous cytotoxic t lymphocytes - A preparation of autologous cytotoxic T-lymphocytes (CTL), specifically reactive to melanoma-associated antigen 3 (MAGE-3), MAGE-4, survivin, human epidermal growth factor receptor 2 (HER2; ERBB2) and cyclooxygenase-2 (COX-2), with potential immunomodulating activity. Peripheral blood mononuclear cells (PBMCs) are collected from the patient. Subsequently, autologous dendritic cells (DCs) are separated, treated with a certain combination of cytokines to produce polarized type-1 DCs (DC1), and then are loaded with MAGE-3/MAGE-4/survivin/HER2/COX-2 CTL epitope peptides. In turn, autologous CTLs are collected, exposed ex vivo to the antigen-loaded DC1s and subsequently expanded in vitro. Upon re-infusion of the DC1-induced MAGE-3/MAGE-4/survivin/HER2/COX-2-specific autologous CTLs, the CTLs target and lyse tumor cells expressing the tumor-associated antigens (TAAs). Exposure to DC1s generates more potent CTLs and thus induces a more potent CTL response against TAA-expressing tumor cells. The targeted TAAs play key roles in cellular proliferation and are overexpressed by a variety of cancer cell types.

• Tyroserleutide - A tripeptide consisting of tyrosine, serine, and leucine with potential antineoplastic activity. Although the mechanism of its antitumor activity has yet to be fully elucidated, tyroserleutide appears to inhibit the expression of ICAM-1 (CD54), a cell adhesion factor of the immunoglobulin (Ig) superfamily that plays an important role in the invasion, adhesion, and metastasis of tumor cells. In addition, this agent may influence the Ca2+/calmodulin pathway, inhibiting phosphatidylinositol 3 kinase (PI3K); PI3K is upregulated in tumor cells and is involved in cellular proliferation.

• Tyrosinase peptide - One of a number of recombinant peptides consisting of amino acid residues of the enzyme tyrosinase, a protein frequently expressed by melanoma cells. Vaccination with tyrosinase peptide may stimulate cytotoxic T lymphocyte response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth.

• Tyrosinase:146-156 peptide - A synthetic peptide consisting of amino acid residues 146 through 156 of the enzyme tyrosinase, a protein frequently expressed by melanoma cells, with antitumor activity. Vaccination with tyrosinase:146-156 peptide may stimulate cytotoxic T lymphocyte response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth and cell lysis.

• Tyrosinase-klh - A peptide vaccine containing a tyrosinase epitope conjugated with keyhole lymphocyte hemocyanin (KLH) with potential antineoplastic activity. Tyrosinase, one of the melanoma differentiation antigens, is the rate-limiting enzyme for melanin synthesis. This tyrosine epitope is conjugated with KLH, which serves as an immunostimulant and a hapten carrier, to enhance immune recognition. Vaccination with tyrosinase-KLH peptide vaccine may produce anti-tyrosinase antibodies as well as elicit a cytotoxic T lymphocyte (CTL) response against cells expressing tyrosinase antigen, resulting in decreased tumor growth.

• Tyrosine kinase inhibitor osi-930 - A selective thiophene-derived tyrosine kinase inhibitor with potential antineoplastic activity. Tyrosine kinase inhibitor OSI-930 inhibits stem cell factor receptor (c-Kit) and the vascular endothelial growth factor receptor 2 (VEGFR2), which may result in the inhibition of both tumor cell proliferation and tumor angiogenesis. Both c-Kit and VEGFR2 are overexpressed in a variety of cancers.

• Tyrosine kinase inhibitor su5402 - An indolinone-based small molecule selective tyrosine kinase inhibitor with potential antineoplastic activity. SU5402 blocks the activities of vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor 1 (FGFR1) via competing with ATP for the specific binding site within the catalytic domain of these receptors. This agent was shown to inhibit cell growth, decrease cell viability in dose-dependent manner, and induce apoptosis.

• Tyrosine kinase inhibitor tl-895 - An orally bioavailable inhibitor of tyrosine kinase, with potential anti-inflammatory and antineoplastic activities. Upon oral administration, tyrosine kinase inhibitor TL-895 targets, binds to, and inhibits tyrosine kinase. This may result in the inhibition of tumor angiogenesis and cell proliferation, and the inhibition of immune-mediated inflammatory processes. Tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis. In addition, they play important roles in the activation of leukocytes and in many immune-mediated inflammatory and autoimmune conditions.

• Tyrosine kinase inhibitor xl228 - A synthetic molecule that targets multiple tyrosine kinases with potential antineoplastic activity. Tyrosine kinase inhibitor XL228 binds to and inhibits the activities of multiple tyrosine kinases, such as the insulin-like growth factor 1 receptor (IGF1R), Src tyrosine kinase, and Bcr-Abl tyrosine kinase. Blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis. In addition, this agent may be a potent inhibitor of the T315I mutant form of the Abl protein, which is associated with the resistance of chronic myelogenous leukemia (CML) to other tyrosine kinase inhibitors. IGF1R and Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis. Bcr-Abl translocation leads to constitutive activation of ABL kinase and is commonly associated with Philadelphia-positive acute lymphocytic leukemia (ALL).

Alphabetic list of antineoplastic agents - 0-9 - A1 - A2 - A3 - A4 - A5 -A6 - B - C - D - E - F - G - H - I - JK - L - M - NO - PQ - R - S - T - UVW - XYZ