Antineoplastic agents a5

• Anti-vegf anticalin prs-050-peg40 - A pegylated, proprietary lipocalin that targets human vascular endothelial growth factor (VEGF), with potential antineoplastic activity. Pegylated anti-VEGF anticalin PRS-050 specifically targets and binds to VEGF receptor 2 (VEGFR2 or KDR), thereby preventing its activity. This may inhibit angiogenesis and eventually reduce tumor cell growth.

• Anti-vegf monoclonal antibody hpv19 - A humanized monoclonal antibody directed against human vascular endothelial growth factor (VEGF), with potential anti-angiogenic and antineoplastic activities. Upon administration, anti-VEGF monoclonal antibody hPV19 targets and binds to VEGFR at a unique binding site and inhibits VEGF binding to its receptors, VEGFR1 and VEGFR2, thereby preventing VEGF/VEGFR-mediated signaling. This prevents the growth and maintenance of tumor blood vessels. This decreases nutrient supply to tumor cells, resulting in tumor cell death. Increased VEGF/VEGFR signaling is associated with increased invasiveness and decreased survival.

• Anti-vegf/ang2 nanobody bi 836880 - A nanobody directed against angiopoietin-2 (Ang2; ANGPT2)- and vascular endothelial growth factor (VEGF)-derived peptides, with potential antiangiogenic and antineoplastic activities. Anti-VEGF/ANG2 nanobody BI 836880 binds to Ang2 and VEGF and inhibits receptor binding; this prevents Ang2- and VEGF-mediated signaling and inhibits both tumor angiogenesis and tumor cell proliferation. Both VEGF and Ang2 are upregulated in a variety of cancer cell types and play a crucial role in angiogenesis. The nanobody is based on functional fragments of single-chain antibodies.

• Anti-vegf/tgf-beta 1 fusion protein hb-002t - A recombinant, human immunoglobulin Fc fusion protein targeting both the transforming growth factor (TGF) beta 1 (TGF-beta 1; TGFb1) and the vascular endothelial growth factor (VEGF), with potential anti-angiogenic and antineoplastic activities. Upon administration of anti-VEGF/TGF-beta 1 fusion protein HB-002T, the fusion protein specifically and selectively targets, binds to and neutralizes both TGF-beta 1 and VEGF. This prevents TGFb1- and VEGF-mediated signaling and abrogates VEGF/VEGFR-induced angiogenesis and TGFb1-mediated induction of VEGF, which further inhibits angiogenesis. It also inhibits TGFb1-mediated immunosuppression, thereby enhancing anti-tumor immunity in the tumor microenvironment (TME) and promoting a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death.

• Anti-vegfc monoclonal antibody vgx-100 - A fully human monoclonal antibody directed against the human vascular endothelial growth factor C (VEGFC or Flt4 ligand) with potential antiangiogenic activity. Anti-VEGFC monoclonal antibody VGX-100 specifically binds to and inhibits VEGFC protein, thereby preventing its binding to VEGFR3 (FLT4) or VEGFR2 (KDR or FLK1). This may prevent VEGFC-mediated signaling and may lead to the inhibition of vascular and lymphatic endothelial cell proliferation. The inhibition of tumor angiogenesis and lymphangiogenesis may eventually decrease tumor cell proliferation and prevent metastasis. VEGFC is overexpressed in a variety of cancer cells, and is associated with increased invasiveness and decreased survival.

• Anti-vegfr2 monoclonal antibody msb0254 - A humanized monoclonal antibody directed against human vascular endothelial growth factor receptor 2 (VEGFR-2; VEGFR2) with potential anti-angiogenesis and antineoplastic activities. Upon administration, anti-VEGFR2 monoclonal antibody MSB0254 specifically binds to and inhibits VEGFR2, which may inhibit tumor angiogenesis and tumor cell proliferation. VEGFR2, a tyrosine-protein kinase that plays an essential role in angiogenesis and the proliferation, survival, migration and differentiation of endothelial cells, is overexpressed in certain tumor types.

• Anti-vegfr2-car retroviral vector-transduced autologous t-lymphocytes - Autologous human CD8-positive T-lymphocytes transduced with a recombinant retroviral vector encoding a chimeric T cell receptor (chimeric antigen receptor or CAR) consisting of an anti-vascular endothelial growth factor receptor type 2 (VEGFR2) scFv (single chain variable fragment), linked to the transmembrane domain of human CD8alpha and coupled to the costimulatory signaling domains of both CD28 and 4-1BB (CD137), and the CD3 zeta chain of the T-cell receptor (TCR), with potential immunostimulating and antineoplastic activities. Autologous peripheral blood lymphocytes (PBLs) from a patient with VEGFR2-positive cancer are pulsed with a retroviral vector that encodes the CAR gene specific for VEGFR2. After expansion in culture and reintroduction into the patient, the anti-VEGFR2 CAR-gene engineered CD8+ lymphocytes express anti-VEGFR2-CAR on their cell surfaces and bind to the VEGFR2 antigen on tumor cell surfaces. Subsequently, VEGFR2-expressing tumor cells are lysed. VEGFR2, a receptor tyrosine kinase (RTK) overexpressed by a variety of cancer cell types, belongs to the VEGFR superfamily and plays key roles in tumor cell proliferation, survival, invasion and tumor angiogenesis. The co-stimulatory molecules are required for optimal T-cell activation.

• Anti-vegfr3 monoclonal antibody imc-3c5 - A fully-human monoclonal antibody directed against human vascular endothelial growth factor receptor 3 (VEGFR-3; Flt-4) with antiangiogenic activity. Anti-VEGFR-3 monoclonal antibody IMC-3C5 specifically binds to and inhibits VEGFR-3, which may result in inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR-3 plays a critical role in the embryonic vascular system development but is restricted postnatally to endothelial cells of lymphatic vessels and found to be expressed in many solid and hematologic malignancies.

• Antrodia cinnamomea supplement - A dietary supplement containing extract from the medicinal fungus Antrodia cinnamomea with potential antiangiogenic, hepatoprotective and antioxidant activities. The components in Antrodia cinnamomea supplement are rather complex, however, rich in triterpenoids, polysaccharides, nucleosides (adenosine) nucleic acids, superoxide dismutase, other small molecular weight proteins and steroid like compounds. Neutral sugars in this supplement show inhibitory activity on endothelial tube formation, while maleimide and maleic anhydride derivative components in the extract, such as antrodin B and antrodin C and their metabolites, exhibit significant cytotoxic effects on tumor cells and hepatitis C virus.

• Antroquinonol capsule - An orally available capsule containing antroquinonol, a farnesylated quinone derivative isolated from the mycelium of Antrodia camphorata, with potential antineoplastic activity. Upon oral administration, antroquinonol binds to and inhibits protein prenylation mediated by the enzymes farnesyltransferase (FTase) and geranylgeranyltransferase 1 (GGTase-1). This prevents both post-translational prenylation and signaling activity of a number of Ras superfamily proteins, such as Ras and Rho. This results in the inhibition of downstream signaling, such as the PI3K/mTOR signaling pathway, and induces apoptosis in susceptible tumor cells. Ras superfamily proteins are overexpressed in numerous cancer cell types, and play a key role in tumor cell proliferation and survival.

• Apalutamide - A small molecule and androgen receptor (AR) antagonist with potential antineoplastic activity. Apalutamide binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells.

• Apatorsen - A second-generation antisense oligonucleotide targeting heat shock protein 27 (Hsp27) with potential antitumor and chemosensitizing activities. Apatorsen suppresses tumor cell expression of Hsp27, which may induce tumor cell apoptosis and enhance tumor cell sensitivity to cytotoxic agents. Hsp27, a chaperone belonging to the small heat shock protein (sHsp) group of proteins, is a cytoprotective protein that supports cell survival under conditions of stress; it has been found to be over-expressed in a variety of human cancers.

• Apaziquone - An indolequinone bioreductive prodrug and analog of mitomycin C with potential antineoplastic and radiosensitization activities. Apaziquone is converted to active metabolites in hypoxic cells by intracellular reductases, which are present in greater amounts in hypoxic tumor cells. The active metabolites alkylate DNA, resulting in apoptotic cell death. This agent displays selectivity activity towards both hypoxic solid tumors, which exhibits higher expression of cytochrome P450 reductase, and well-oxygenated malignant cells that overexpress the bioreductive enzyme NQO1 (NAD(P)H: quinone oxidoreductase). Apaziquone may selectively sensitize hypoxic tumor cells to radiocytotoxicity.

• Apc8015f - A cell-based vaccine composed of previously frozen autologous antigen-presenting peripheral blood mononuclear cells (enriched for a dendritic cell fraction) that have been exposed to a recombinant protein consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to prostatic-acid phosphatase (PAP), a protein expressed by prostate cancer cells. Upon administration, the vaccine may stimulate an antitumor T-cell response against tumor cells expressing PAP.

• Ape1/ref-1 redox inhibitor apx3330 - An orally bioavailable inhibitor of apurinic/apyrimidinic endonuclease 1/reduction-oxidation (redox) effector factor-1 (APE1/Ref-1; APEX1), with potential anti-angiogenic and antineoplastic activities. Upon administration, the APE1/Ref-1 Inhibitor APX3330 selectively targets and binds to APE1/Ref-1. This inhibits the redox-dependent signaling activity of APE1/Ref-1, by preventing the reduction and activation of numerous APE1/Ref-1-dependent oncogenic transcription factors (TFs), such as nuclear factor kappa B (NF-kB), AP-1, STAT3, p53, NRF2 and HIF-1alpha, that are involved in signaling, cell proliferation, tumor progression and survival of cancer cells. Therefore, this agent inhibits the activation of multiple TF-mediated signaling pathways and inhibits tumor cell proliferation and survival. APE1/Ref-1, a multifunctional protein overexpressed in many cancer cell types, plays a key role as a redox regulator of transcription factor activation and in base excision repair upon DNA damage. It drives cancer cell proliferation, migration, drug resistance, angiogenesis and inflammation and its expression level correlates with increased tumor aggressiveness and decreased patient survival. APX3330 specifically blocks the redox activity of APE1/Ref-1 and does not affect its ability to act as a DNA repair endonuclease.

• Aphidicoline glycinate - A tetracyclic diterpene antibiotic isolated from the fungus Cephalosporium aphidicola and other fungal species with potential antineoplastic activity. Aphidicoline glycinate blocks the cell cycle at early S-phase by specifically inhibiting DNA polymerases in eukaryotic cells, induces apoptosis, and stops the growth of eukaryotic cells and certain viruses by selectively inhibiting DNA polymerase II or viral-induced DNA polymerases.

• Apilimod dimesylate capsule - A capsule containing the dimesylate salt form of apilimod, an inhibitor of the class III PI kinase phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), with potential antineoplastic and immunomodulatory activities. Upon oral administration of apilimod dimesylate capsule, apilimod selectively binds to and inhibits PIKfyve. The inhibition leads to disruption of PIKfyve-mediated signal transduction pathways and eventually inhibits tumor cell growth in PIKfyve-overexpressing tumor cells. Also, PIKfyve inhibition by apilimod inhibits the toll-like receptor (TLR)-induced production of various cytokines, including interleukin-12 (IL-12) and IL-23, thereby preventing IL-12/IL-23-mediated immune responses. PIKfyve, a lipid kinase dysregulated in various tumor types, plays a key role in TLR signaling and tumor cell migration, proliferation and survival.

• Apitolisib - An orally available agent targeting phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. Apitolisib inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion.

• Apolizumab - A humanized monoclonal antibody directed against 1D10, a polymorphic determinant on the HLA-DR beta chain that is expressed on normal and neoplastic B cells. Apolizumab induces complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen-positive B cells in vitro.

• Apomab - A fully human monoclonal antibody directed against human death receptor 5 (DR5; TRAIL-R2; TNFRSF10B) with potential pro-apoptotic and antineoplastic activities. Mimicking the natural ligand TRAIL (tumor necrosis factor-related apoptosis inducing ligand), apomab binds to DR5, which may directly activate the extrinsic apoptosis pathway and indirectly induce the intrinsic apoptosis pathway in tumor cells. DR5 is a cell surface receptor of the TNF-receptor superfamily and is expressed in a broad range of cancers.

• Apomine - A 1,1-bisphosphonate ester with potential antineoplastic and hypocholesterolemic activities. SR-45023A binds to hydroxyapatite crystals in the bone matrix where it inhibits enzymatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for the formation of mevalonate, the precursor of cholesterol. Consequently, shortage of mevalonate impedes the synthesis of downstream isoprenoids that are essential for protein prenylation. This leads to the loss of activity of proteins involved in osteoclast function and cellular proliferation, such as Ras and Rho, leading to an inhibition of cellular proliferation, and induction of osteoclasts apoptosis. In addition, SR-45023A activates the farnesoid X activated receptor (FXR), a member of the nuclear hormone superfamily implicated in cholesterol metabolism and bile acid transport and may play a role in this agent's antineoplastic effect.

• Apoptosis inducer bzl101 - An orally active aqueous extract derived from the plant Scutellaria barbata with potential antineoplastic activity. Sparing normal cells, apoptosis inducer BZL101 specifically facilitates translocation of the protein apoptosis-inducing factor (AIF) from the mitochondrial membrane into the nucleus in tumor cells, thereby causing tumor cell-specific chromatin condensation and DNA degradation followed by the induction of caspase-independent apoptosis. AIF is both a mitochondrial intermembrane flavoprotein with oxidoreductase activity and a caspase-independent death effector that, similar to cytochrome c, is released from mitochondria early in the apoptotic process.

• Apoptosis inducer gcs-100 - A galectin-binding polysaccharide derived from citrus pectin with potential antineoplastic activity. Apoptosis inducer GCS-100 binds to the carbohydrate-binding domain of the lectin galectin-3, which may result in apoptosis mediated through mitochondria/caspase activation cascades; this agent may overcome tumor growth mediated through anti-apoptotic protein Bcl-2, heat-shock protein 27 (Hsp27), and nuclear factor-kappa B (NF-kB). Galectin-3, a chimeric molecule consisting of both carbohydrate recognition and collagen-like domains, interacts with a variety of carbohydrate and protein ligands to form pentamers with unique crosslinking abilities; this lectin also exhibits anti-apoptotic properties, perhaps, in part, through the regulation of intracellular signaling pathways.

• Apoptosis inducer mpc-2130 - A broad-acting, apoptosis-inducing, small molecule with potential antineoplastic activity. Although the exact mechanism of action has yet to be fully elucidated, apoptosis inducer MPC-2130 exhibits proapoptotic activities in tumor cells, including membrane phosphatidylserine externalization, release of cytochrome C from mitochondria, caspase activation, cell condensation, and DNA fragmentation. In addition, because this agent is not a substrate for several types of multidrug resistance (MDR) ABC superfamily transporters, such as P-glycoprotein 1 (MDR-1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1/ABCG2), it may be useful in treating MDR tumors that express these particular MDR efflux pumps.

• Apoptotic autologous tumor cells-pulsed alpha-type-1 polarized dendritic cells - A cell based cancer vaccine composed of mature polarized dendritic cells (DCs) and pulsed with apoptotic autologous tumor cells that has potential immunostimulating and antineoplatic activities. Dendritic cells (DCs) were treated with interleukin-1beta, tumor necrosis factor alpha, interferon-alpha (IFN-a), IFN-gamma and polyinosinic:polycytidylic acid (p-I:C) to produce mature alpha type-1 polarized DCs (alphaDC1) that are capable of producing high levels of interleukin-12p70 (IL-12p70). The alphaDC1 are subsequently pulsed with apoptotic autologous tumor cells. Upon administration, these DCs are able to induce a potent cytotoxic T lymphocyte (CTL) response against tumor associated antigens (TAAs), resulting in tumor cell lysis and inhibition of tumor cell growth. Apoptotic tumor cells contain an array of TAAs.

• Apricoxib - An orally bioavailable nonsteroidal anti-inflammatory agent (NSAID) with potential antiangiogenic and antineoplastic activities. Apricoxib binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), thereby inhibiting the conversion of arachidonic acid into prostaglandins. Apricoxib-mediated inhibition of COX-2 may induce tumor cell apoptosis and inhibit tumor cell proliferation and tumor angiogenesis. COX-related metabolic pathways may represent crucial regulators of cellular proliferation and angiogenesis.

• Aprinocarsen - A synthetic phosphorothioate oligodeoxynucleotide. As an antisense molecule, aprinocarsen hybridizes to the 3-untranslated region of the human protein kinase C (PKC-alpha) mRNA, thereby inhibiting PKC-alpha expression and growth of PKC-alpha-dependent tumor cells.

• Aprutumab - An antibody against the fibroblast growth factor receptor type 2 (FGFR2), with potential antineoplastic activity. Upon administration, aprutumab binds to and inhibits FGFR2, which may result in the inhibition of both FGFR2 phosphorylation and FGFR2-mediated signal transduction pathways. This results in the inhibition of cell proliferation and the induction of cell death of FGFR2-expressing tumor cells. FGFR2, upregulated in many tumor cell types, is a receptor tyrosine kinase, which is essential to tumor cellular proliferation, differentiation and survival.

• Aprutumab ixadotin - An antibody-drug conjugate (ADC) directed against the fibroblast growth factor receptor type 2 (FGFR2) and conjugated to an as of yet unidentified toxin, with potential antineoplastic activity. Upon intravenous administration, aprutumab ixadotin binds to FGFR2. Upon binding, the toxin selectively induces cell death, through an as of yet undisclosed mechanism of action, in FGFR2-expressing tumor cells. FGFR2, a receptor tyrosine kinase upregulated in many tumor cell types, plays an essential role in tumor cell proliferation, differentiation and survival.

• Ar antagonist bms-641988 - An androgen receptor (AR) antagonist with potential antineoplastic and anti-androgenic activities. BMS-641988 binds to the androgen receptor in target tissues, thereby preventing androgen-induced receptor activation, and facilitates the formation of inactive complexes that cannot be translocated to the nucleus. This may inhibit androgen-dependent gene expression, subsequently leading to an inhibition of cell growth and apoptosis in AR-expressing cells.

• Arabinoxylan compound mgn3 - An arabinoxylane polysaccharide composed of the hemicellulose-Beta extract of rice bran, treated with enzymes from Shiitake mushrooms, that exerts antitumor and antiviral activity by increasing the level of natural killer cells activation. (NCI)

• Aranose - A nitrosourea derivative with potential antineoplastic activity. Upon administration, aranose alkylates and crosslinks DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest and apoptosis.

• Arc fusion protein sl-279252 - An agonist redirected checkpoint (ARC) fusion protein consisting of the extracellular domains of human programmed cell death 1 (PD-1; PDCD1; CD279) and tumor necrosis factor ligand superfamily member 4 (TNFSF4; OX40 ligand; OX40L; CD252), linked by a central Fc domain (PD1-Fc-OX40L), with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, ARC fusion protein SL-279252 simultaneously binds to both tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40) and PD-1 expressed on T-lymphocytes. Stimulation of OX40 may promote cytokine production and induce proliferation of memory and effector T-lymphocytes against tumor cells, while PD-1 binding disrupts PD-1 signaling and may restore immune function through the activation of T-cells. This may enhance the immune-mediated elimination of tumor cells more effectively than PD-1 blockade or OX40-agonism alone. OX40L, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) ligand family, provides a co-stimulatory signal for the proliferation and survival of activated T-cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T-cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death-1 ligand 1 (PD-L1; CD274) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity.

• Archexin - A 20-mer antisense oligodeoxynucleotide (ODN) against the proto-oncogene Akt with potential antineoplastic activity. Akt-1 antisense oligonucleotide RX-0201 binds to Akt-1 mRNA, inhibiting translation of the transcript; suppression of Akt-1 expression may result in the inhibition of cellular proliferation and the induction of apoptosis in tumor cells that overexpress Akt-1. Akt-1 is a serine-threonine protein kinase that stimulates proliferation and inhibits apoptosis of tumor cells.

• Arcitumomab - A murine IgG monoclonal Fab' fragment antibody directed against carcinoembryonic antigen (CEA), a protein that is overexpressed by many tumor cell types. For tumors that overexpress CEA, technetium-99m labeled arcitumomab may be used as an adjunct diagnostic imaging tool to obtain prognostic information following resection and to monitor for recurrent disease.

• Arfolitixorin - The R-isomer of folitixorin, a reduced folate-based biomodulator and active metabolite of folate drugs leucovorin (LV) and levoleucovorin (l-LV) that can be used to increase the efficacy of certain antimetabolites, such as the cytotoxic agent 5-fluorouracil (5-FU), and reduce as well as protect against certain antimetabolite-associated adverse effects, such as those seen with high-dose (HD) methotrexate. Upon administration of arfolitixorin, 5,10-methylenetetrahydrofolate (MTHF) is a reduced folate substrate for the enzyme thymidylate synthase (TS) and stabilizes, upon co-administration of 5-FU, the covalent binding of the 5-FU metabolite 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP), instead of deoxyuridine monophosphate (dUMP), to its target enzyme TS, which results in an inhibition of TS. This inhibits the synthesis of deoxythymidine monophosphate (dTMP) and leads to the depletion of thymidine triphosphate (TTP), which is a necessary constituent of DNA. This inhibits DNA synthesis, which leads to an inhibition of cellular proliferation and induces tumor cell death. As MTHF is able to stabilize and strengthen the ternary complex, co-administration of arfolitixorin enhances the inhibition of DNA synthesis and increases the cytotoxic effect of 5-FU. As MTHF is the active form of folate and the active metabolite of LV and l-LV, arfolitixorin does not need to be converted to an active metabolite to become activated. In DNA synthesis, a ternary complex is formed between the reduced folate substrate MTHF, the TS enzyme and dUMP in order to convert dUMP to the DNA building block dTMP, which is necessary for DNA synthesis.

• Arginase-1 peptide vaccine - A vaccine comprised of arginase-1 peptides, with potential antineoplastic activity. Upon vaccination, the arginase-1 peptide vaccine may activate the immune system to induce an immune response against arginase-1-expressing cells. Arginase-1 is expressed by some cancer cells and by immune inhibitory cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs); its expression is associated with poor prognosis.

• Arginine butyrate - The butyric acid salt of the amino acid arginine. In EBV-related lymphomas, arginine butyrate induces EBV thymidine kinase transcription and may act synergistically with the antiviral agent ganciclovir to inhibit cell proliferation and decrease cell viability. In addition, the butyrate moiety inhibits histone deacetylase, which results in hyperacetylation of histones H3 and H4. Acetylated histones have a reduced affinity for chromatin; this reduced histone-chromatin affinity may allow chromosomal unfolding, potentially enhancing the expression of genes related to tumor cell growth arrest and apoptosis.

• Arnebia indigo jade pearl topical cream - A proprietary multiherbal topical cream based on Chinese herbal medicine with potential antineoplastic, antiviral, antibacterial and immunostimulatory activities. Arnebia Indigo Jade Pearl topical cream contains 12 ingredients including 9 herbs infused in sesame oil, with an additional three powdered ingredients and beeswax added to the infused oil to create the salve. The purported mechanism(s) of action is unclear due to the complexity of the herbal mixture.

• Arsenic trioxide - A small-molecule arsenic compound with antineoplastic activity. The mechanism of action of arsenic trioxide is not completely understood. This agent causes damage to or degradation of the promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARa) fusion protein; induces apoptosis in acute promyelocytic leukemia (APL) cells and in many other tumor cell types; promotes cell differentiation and suppresses cell proliferation in many different tumor cell types; and is pro-angiogenic.

• Arsenic trioxide capsule formulation orh 2014 - An orally bioavailable capsule formulation of the inorganic toxic compound arsenic trioxide (As2O3), with potential antineoplastic activity. Although the mechanism of action (MoA) of As2O3 is not well understood, upon oral administration of ORH 2014, As2O3 appears to bind to DNA, prevent DNA synthesis, and cause DNA fragmentation, which leads to an induction of apoptosis in proliferating cells, including tumor cells. In addition, As2O3 causes damage to and induces degradation of the promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARa) fusion protein, and inhibits the activity of the enzyme thioredoxin reductase.

• Artemether sublingual spray - A sublingual spray containing artemether, a semisynthetic derivative of artemisinin, an endoperoxide extracted from the Chinese herb qinghaosu (Artemisia annua or annual wormwood), with antiparasitic and potential antineoplastic activity. Upon sublingual application of the spray, artemether exerts its antineoplastic activity through as of yet not fully elucidated mechanism(s) of action. This agent binds to heme molecules inside cells, thereby inducing reactive oxygen species (ROS)-mediated damage which selectively kills cancer cells. In addition, artemether appears to target and modulate the expression of various proteins involved in cancer cell proliferation, angiogenesis, invasion and metastasis. Also, this agent depletes T regulatory cells, and modulates the production of inflammatory cytokines, such as interleukin-4 and interferon-gamma. Altogether, this inhibits tumor cell proliferation. The sublingual spray allows faster absorption of a higher percentage of the artemether dose, when compared to the oral form, as it avoids first pass metabolism; this results in an increased efficacy.

• Artemisinin dimer - A sesquiterpene lactone peroxide and dimerized plant product derived from Artemisia annua L with anti-malarial, anti-proliferative and anti-angiogenic effects. Artemisinin contains an endoperoxide moiety which forms free radicals when it reacts with iron. The resultant carbon-based radical can lead to cellular damage and cell death by reacting with cellular macromolecules such as proteins and membrane lipids. Malaria parasites contain large amounts of heme-iron, a product from the digestion of hemoglobin. However, recently it has been suggested that activation of artemisinin inside the parasite is by ferrous iron. Furthermore, due to their rapid rate of division, cancer cells require and uptake a large amount of iron to proliferate, therefore they are more susceptible to the cytotoxic effect of artemisinin than non-cancerous cells. The dimer configuration has been shown to increase compound stability and reduce general toxicity.

• Artesunate - A water-soluble, semi-synthetic derivative of the sesquiterpine lactone artemisinin with anti-malarial, anti-schistosomiasis, antiviral, and potential anti-neoplastic activities. Upon hydrolysis of artesunate's active endoperoxide bridge moiety by liberated heme in parasite-infected red blood cells, reactive oxygen species and carbon-centered radicals form, which have been shown to damage and kill parasitic organisms. Additionally, in vitro studies demonstrate that this agent induces DNA breakage in a dose-dependent manner. Artesunate has also been shown to stimulate cell differentiation, arrest the cell cycle in the G1 and G2/M phases, inhibit cell proliferation, and induce apoptosis through mitochondrial and caspase signaling pathways. Artemisinin is isolated from the plant Artemisia annua.

• Arugula seed powder - A dietary supplement containing an extract powder derived from the seeds of the cruciferous vegetable arugula (Eruca sativa), with potential chemopreventive and antioxidant activities. Arugula seed powder contains numerous vitamins and minerals, and is rich in phytonutrients, such as sulforaphane and indole-3-carbinol. Although the exact mechanism of action through which arugula seed powder may exert its anti-tumor effect has yet to be fully elucidated, the effects of this powder on cancer cells may be attributable to the antioxidant and pro-apoptotic activities of the phytonutrients.

• Aryl hydrocarbon receptor antagonist bay2416964 - An orally available formulation containing a small molecule antagonist of the aryl hydrocarbon receptor (AhR; class E basic helix-loop-helix protein 76; bHLHe76) with potential immunomodulating and antineoplastic activities. Upon oral administration, AhR antagonist BAY2416964 specifically binds to AhR, inhibits AhR activation, and prevents AhR-mediated signaling. Abrogation of AhR activation prevents the activation of immune-tolerant dendritic cells (DCs) and regulatory T-cells (Tregs) in the tumor microenvironment (TME). This may restore the immune response against tumor cells. AhR, a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, has important roles in regulating immunity and cellular differentiation. AhR can exhibit both pro-oncogenic and tumor suppressor-like functions depending on the tumor type; therefore, its expression may serve as a negative or positive prognostic factor.

• Aryl hydrocarbon receptor inhibitor ik-175 - An orally bioavailable selective inhibitor of the aryl hydrocarbon receptor (AhR; class E basic helix-loop-helix protein 76; bHLHe76), with potential immunomodulating and antineoplastic activities. Upon oral administration, AhR inhibitor IK-175 specifically targets and binds to AhR, inhibits AhR activation, prevents AhR-mediated signaling, and AhR-dependent tumor cell proliferation. Abrogation of AhR activation prevents the activation of immune-tolerant dendritic cells (DCs), regulatory T-cells (Tregs) and decreases suppressive cytokines in the tumor microenvironment (TME). It stimulates cytotoxic T-cell activation and expansion. This may restore the immune response against tumor cells. AhR, a member of the basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, plays key roles in regulating immunity and cellular differentiation. It mediates the expression of multiple immune related and tumor cell signal transduction and proliferation genes.

• Asaley - An L-leucine derivative of melphalan with antineoplastic activity. Asaley alkylates and crosslinks DNA, resulting in disruption of DNA synthesis.

• Asciminib - An orally bioavailable, allosteric Bcr-Abl tyrosine kinase inhibitor with potential antineoplastic activity. Designed to overcome resistance, ABL001 binds to the Abl portion of the Bcr-Abl fusion protein at a location that is distinct from the ATP-binding domain. This binding results in the inhibition of Bcr-Abl-mediated proliferation and enhanced apoptosis of Philadelphia chromosome-positive (Ph+) hematological malignancies. The Bcr-Abl fusion protein tyrosine kinase is an abnormal enzyme produced by leukemia cells that contain the Philadelphia chromosome.

• Ascrinvacumab - A fully human, IgG2 monoclonal antibody directed against activin-like receptor kinase 1 (ALK-1) with potential antineoplastic activity. Ascrinvacumab binds to and neutralizes ALK-1. This may disrupt tumor endothelial cell function and inhibit tumor angiogenesis, eventually leading to an inhibition of tumor cell proliferation. ALK-1, a member of the transforming growth factor beta (TGF-b) type I receptor family, is overexpressed on endothelial cells in a variety of tumor cell types and increases endothelial cell proliferation and migration.

• Ashwagandha root powder extract - A dietary supplement containing an extract powder derived from the root of the ashwagandha shrub with potential antineoplastic, antioxidant, immunostimulating and anti-angiogenic activities. Ashwagandha root powder extract contains numerous alkaloids, including withanine as the primary alkaloid, and steroidal lactone withanolides. The withanolides in this agent may suppress nuclear factor-kappaB activation and nuclear factor-kappaB-regulated gene expression, potentiating apoptosis and inhibiting tumor cell invasion. Cultivated in India and North America, ashwagandha (Withania somnifera Dunal or Indian ginseng) belongs to the Solanaceae (nightshade) family.

• Asp4132 - A molecule with potential antineoplastic activity. Upon oral administration, ASP4132 affects oxidative phosphorylation in mitochondria of metabolically-active tumor cells, which reduces both energy production and tumor cell proliferation. Mitochondrial oxidative phosphorylation is hyperactivated in tumor cells and plays a key role in the promotion of tumor cell proliferation.

• Aspacytarabine - A small molecule pro-drug consisting of cytarabine, an antimetabolite analog of cytidine with a modified arabinose sugar moiety, covalently bonded to asparagine, with potential antineoplastic activity. Upon intravenous administration, aspacytarabine targets cancer cells, which often lack asparagine synthetase and are dependent on an external source of amino acids due to their high metabolic rate. Once the prodrug is inside target cells, the cytarabine component is cleaved and competes with cytidine for incorporation into DNA. The arabinose sugar moiety of cytarabine sterically hinders the rotation of the molecule within DNA, resulting in cell cycle arrest, specifically during the S phase of replication. Cytarabine also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Because BST-236 specifically targets cancer cells, it may spare normal tissues from cytarabine-related toxicities.

• Asparaginase - An enzyme isolated from the bacterium Escherichia coli or the bacterium Erwinia carotovora with antileukemic activity. Asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia in leukemic cells, resulting in the depletion of asparagine, inhibition of protein synthesis, cell cycle arrest in the G1 phase, and apoptosis in susceptible leukemic cell populations. Asparagine is critical to protein synthesis in leukemic cells; some leukemic cells cannot synthesize this amino acid de novo due to the absent or deficient expression of the enzyme asparagine synthase. The E. carotovora-derived form of asparaginase is typically reserved for cases of asparaginase hypersensitivity.

• Asparaginase erwinia chrysanthemi - An enzyme isolated from the bacterium Erwinia chrysanthemi (E. carotovora). Asparagine is critical to protein synthesis in leukemic cells, which cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. Asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting leukemic cells of asparagine and blocking protein synthesis and tumor cell proliferation, especially in the G1 phase of the cell cycle. This agent also induces apoptosis in tumor cells. The Erwinia-derived product is often used for those patients who have experienced a hypersensitivity reaction to the E. Coli formulation.

• Aspirin - An orally administered non-steroidal antiinflammatory agent. Acetylsalicylic acid binds to and acetylates serine residues in cyclooxygenases, resulting in decreased synthesis of prostaglandin, platelet aggregation, and inflammation. This agent exhibits analgesic, antipyretic, and anticoagulant properties.

• Astatine at 211 anti-cd38 monoclonal antibody okt10-b10 - A radioimmunoconjugate composed of the anti-CD38 monoclonal antibody (MoAb) OKT10-B10 labeled with the alpha-emitting radionuclide astatine (At) 211 (211At), with potential antineoplastic activity. Upon administration of astatine At 211 anti-CD38 MoAb OKT10-B10, the MoAb moiety targets and binds to CD38-expressing tumor cells, thereby delivering a cytotoxic dose of alpha radiation directly to the CD38-expressing tumor cells. CD38, a type II transmembrane glycoprotein and tumor-associated antigen (TAA), is present on various immune cells and in hematologic malignancies; its expression has been correlated with poor prognosis.

• Astatine at 211 anti-cd45 monoclonal antibody bc8-b10 - A radioimmunoconjugate containing the murine IgG1 anti-CD45 monoclonal antibody (MAb) BC8 where the lysine side groups have been conjugated with decaborate (closo-decaborate; B10) and labeled with astatine (At) 211, with potential immunotherapeutic activity. Astatine At 211 anti-CD45 monoclonal antibody BC8-B10 binds to CD45 antigen, a receptor protein-tyrosine phosphatase expressed on the surface of both normal and malignant hematopoietic cells. After binding and internalization by CD45-expressing tumor cells, this agent may deliver a cytotoxic dose of alpha radiation. Additionally, the radiolabel can be leveraged to assay the biodistribution and/or pharmacokinetics (absorption, distribution, metabolism and excretion) for this agent. The use of B10 rather than other labeling methods increases the therapeutic efficacy while decreasing the toxicity of the radioconjugate.

• Astuprotimut-r - A cancer vaccine consisting of a recombinant form of human melanoma antigen A3 (MAGE-A3) combined with a proprietary adjuvant with potential immunostimulatory and antineoplastic activities. Upon administration, astuprotimut-R may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the MAGE-A3 antigen, resulting in tumor cell death. MAGE-A3, a tumor-associated antigen (TAA) originally discovered in melanoma cells, is expressed by various tumor types. The proprietary immunostimulating adjuvant in this agent is composed of a specific combination of immunostimulating compounds selected to increase the anti-tumor immune response to MAGE-A3.

• Asulacrine - An amsacrine analogue with antineoplastic properties. Asulacrine inhibits the enzyme topoisomerase ll, thereby blocking DNA replication and RNA and protein synthesis.

• Asulacrine isethionate - The isethionate salt of an amsacrine analogue with antineoplastic properties. Asulacrine inhibits the enzyme topoisomerase ll, thereby blocking DNA replication and RNA and protein synthesis.

• Asunercept - A human, soluble fusion protein consisting of the extracellular domain of the CD95 receptor fused to the Fc-domain of the human IgG antibody, with potential antineoplastic activity. Upon administration, asunercept binds to the CD95 ligand (CD95L) and blocks the binding of CD95L to the CD95 receptor. In tumor cells, blockage of CD95L-mediated signaling pathways may prevent cell migration and invasive cell growth; in healthy cells, blockage of CD95L-mediated signaling pathways may prevent apoptosis and may protect cell damage. Activation of the CD95 receptor plays an important role in the initiation of apoptosis in healthy cells or the invasive growth of cancer cells.

• At 211 monoclonal antibody 81c6 - A radioimmunoconjugate of a human-murine chimeric IgG2 monoclonal antibody (MoAb) 81C6 labeled with an alpha-emitting radionuclide Astatine 211 (At-211), with imaging and radioimmunotherapeutic properties. MoAb 81C6 recognizes the extracellular matrix antigen tenascin (hexabrachion), which is up-regulated in gliomas and other cancers. Using MoAb 81C6 as a carrier for At-211 results in the targeted imaging and/or destruction of cells expressing tenascin.

• Atamestane - A synthetic steroidal substance with antineoplastic activity. Atamestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens.

• Atezolizumab - A humanized, Fc optimized, monoclonal antibody directed against the protein ligand PD-L1 (programmed cell death-1 ligand 1), with potential immune checkpoint inhibitory and antineoplastic activities. Atezolizumab binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1) expressed on activated T-cells, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. In addition, by binding to PD-L1, MPDL3280A also prevents binding of this ligand to B7.1 expressed on activated T cells, which further enhances the T-cell-mediated immune response. PD-L1 is overexpressed on many human cancer cell types and on various tumor-infiltrating immune cells. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in increased immune evasion. PD-1, a transmembrane protein, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T cells. The Fc region of MPDL3280A is modified in such a way that it does not induce either antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).

• Atiprimod - An orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and antiangiogenic properties. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3), blocking the signalling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1, thereby inhibiting cell proliferation, inducing cell cycle arrest, and inducing apoptosis.

• Atiprimod dihydrochloride - The dihydrochloride salt form of atiprimod, an orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and anti-angiogenic activities. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AKT, blocking the signaling pathways of interleukin-6, vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1. This results in the inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis.

• Atiprimod dimaleate - The dimaleate salt form of atiprimod, an orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and antiangiogenic activities. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AKT, blocking the signaling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1. This results in the inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis.

• Atm inhibitor m 3541 - An orally bioavailable inhibitor of ataxia telangiectasia mutated kinase (ATM), with potential chemo-/radio-sensitizing and antineoplastic activities. Upon oral administration, M 3541 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. In addition, M 3541 sensitizes tumor cells to chemo- and radiotherapy. ATM, a serine/threonine protein kinase, is upregulated in a variety of cancer cell types; it is activated in response to DNA damage and plays a key role in DNA-strand repair.

• Atm kinase inhibitor azd0156 - An orally bioavailable ataxia telangiectasia mutated (ATM) kinase inhibitor, with potential chemo-/radio-sensitizing and antineoplastic activities. Upon oral administration, AZD0156 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. In addition, AZD0156 sensitizes tumor cells to chemo- and radiotherapy. ATM, a serine/threonine protein kinase, is upregulated in a variety of cancer cell types; it is activated in response to DNA damage and plays a key role in DNA-strand repair.

• Atm kinase inhibitor azd1390 - An orally bioavailable inhibitor of ataxia telangiectasia mutated (ATM) kinase, with potential antineoplastic activity. Upon oral administration, AZD1390 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death in ATM-overexpressing tumor cells. AZD1390 hypersensitizes tumors to chemo/radiotherapy. In addition, AZD1390 is able to cross the blood-brain barrier (BBB). ATM, a serine/threonine protein kinase belonging to the phosphatidylinositol 3-kinase-related kinase (PIKK) family of protein kinases, is upregulated in a variety of cancer cell types. It is activated in response to DNA double-strand breaks (DSB) and plays a key role in DNA repair.

• Atorvastatin calcium - The calcium salt of atorvastatin, a synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent increases the number of LDL receptors on hepatic cell surfaces, enhancing the uptake and catabolism of LDL and reducing LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also display direct antineoplastic activity, possibly by inhibiting farnesylation and geranylgeranylation of proteins such as small GTP-binding proteins, which may result in the arrest of cells in the G1 phase of the cell cycle. This agent may also sensitize tumor cells to cyctostatic drugs, possibly through the mTOR-dependent inhibition of Akt phosphorylation.

• Atorvastatin sodium - The sodium salt of atorvastatin, a synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent increases the number of LDL receptors on hepatic cell surfaces, enhancing the uptake and catabolism of LDL and reducing LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also display direct antineoplastic activity, possibly by inhibiting farnesylation and geranylgeranylation of proteins such as small GTP-binding proteins, which may result in the arrest of cells in the G1 phase of the cell cycle. This agent may also sensitize tumor cells to cyctostatic drugs, possibly through the mTOR-dependent inhibition of Akt phosphorylation.

• Atr inhibitor rp-3500 - An orally available inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase, with potential antineoplastic activity. Upon oral administration, ATR inhibitor RP-3500 selectively targets and inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase checkpoint kinase 1 (CHK1). This prevents ATR-mediated signaling, which results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and survival. It is activated by DNA damage caused during DNA replication-associated stress.

• Atr kinase inhibitor bay1895344 - An orally available ataxia telangiectasia and Rad3-related (ATR)-specific kinase inhibitor, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor BAY1895344 selectively binds to and inhibits the activity of ATR, which prevents ATR-mediated signaling. This inhibits DNA damage checkpoint activation, disrupts DNA damage repair and induces apoptosis in ATR-overexpressing tumor cells. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and cell survival.

• Atr kinase inhibitor m1774 - An orally available inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor M1774 selectively inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase checkpoint kinase 1 (CHK1). This prevents ATR-mediated signaling, which results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and survival. It is activated by DNA damage caused during DNA replication-associated stress.

• Atr kinase inhibitor vx-803 - An orally available inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor VX-803 selectively inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase CHK1. This prevents ATR-mediated signaling, which results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and survival; it is activated by DNA damage caused during DNA replication-associated stress.

• Atrasentan hydrochloride - The orally available hydrochloride salt of pyrrolidine-3-carboxylic acid with potential antineoplastic activity. As a selective antagonist of the endothelin-A (ETA) receptor, atrasentan binds selectively to the ETA receptor, which may result in inhibition of endothelin-induced angiogenesis and tumor cell proliferation.

• Attenuated chimpanzee adenovirus 5t4 vaccine - A cancer vaccine comprised of a recombinant, attenuated, replication-defective simian adenovirus vector (ChAdOx1) encoding the human 5T4 fetal oncoprotein (ChAdOx1.5T4), with potential immuno-activating and antineoplastic activities. Upon administration of the recombinant attenuated chimpanzee adenovirus 5T4 vaccine, the viral vector expresses 5T4 and stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing 5T4, which results in tumor cell lysis. 5T4, a transmembrane glycoprotein, is overexpressed by a variety of cancer cell types; its expression is correlated with increased invasiveness.

• Attenuated corynebacterium parvum - A heat-inactivated preparation of Corynebacterium parvum with immunoadjuvant properties. Therapeutic Corynebacterium parvum may stimulate host antitumor immune responses when added to cancer vaccines.

• Attenuated listeria monocytogenes crs-100 - A live-attenuated strain of the Gram-positive bacterium Listeria monocytogenes (Lm) with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, attenuated Listeria monocytogenes CRS-100 may accumulate in and infect liver cells where it may activate a potent innate immune response and an adaptive immune response involving the by recruitment and activation of T lymphocytes. This agent may potentiate the immune response to vaccines against various liver neoplasms.

• Attenuated live listeria monocytogenes encoding kras g12d - An off-the-shelf, plasmid DNA-based cancer vaccine composed of a live-attenuated strain of the Gram-positive bacterium Listeria monocytogenes (Lm) carrying a plasmid vector encoding multiple, not yet disclosed, tumor associated antigens (TAAs) and sequence peptides associated with commonly occurring hotspot mutations, including the aspartic acid substitution for glycine at position 12 (G12D) in KRAS, with potential immunostimulatory and antineoplastic activities. Upon administration, ADXS-503 is taken up by antigen presenting cells (APCs) and the TAAs are processed and presented to immune cells by both major histocompatibility complex (MHC) I and II molecules. This leads to an increase in antigen-specific CD8-positive T-cells and gamma/delta T-cells within the tumor microenvironment (TME) and an inhibition of immunosuppressive tumor-infiltrating T-regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This may lead to tumor cell death in cells expressing TAAs that are shared across multiple tumor types. The KRAS G12D mutation is thought to drive tumorigenesis and progression in some cancers.

• Attenuated measles virus encoding scd transgene tmv-018 - A recombinant, attenuated oncolytic measles virus (MV) encoding the prodrug converting enzyme super cytosine deaminase (SCD), that can potentially be used as an antineoplastic adjuvant and with potential antineoplastic activity. Upon intra-tumoral injection, TMV-018 preferentially enters and transfects tumor cells, and expresses SCD, an enzyme that catalyzes the intracellular conversion of the prodrug flucytosine (5-fluorocytosine; 5-FC) into the antineoplastic agent 5-fluorouracil (5-FU). After administration of 5-FC, the tumor can be eradicated upon activation of 5-FU by SCD. In addition, the oncolytic MV may infect and lyse tumor cells. In turn, the lysed tumor cells release various tumor-associated antigens (TAAs), which induce an immune response against the tumor cells. This may further eradicate tumor cells.

• Atuveciclib - An inhibitor of positive transcription elongation factor b (P-TEFb), which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin-T (CycT), with potential antineoplastic activity. Upon administration, atuveciclib binds to and inhibits the activity of P-TEFb, thereby preventing the phosphorylation of its downstream target, the carboxyl terminal domain (CTD) of RNA polymerase II (RNA Pol II), and inhibiting the activation of transcriptional elongation by RNA Pol II. This prevents the transcription of tumor promoting genes, induces tumor cell apoptosis, and inhibits tumor cell proliferation. P-TEFb plays an important role in the regulation of gene transcription; over-activation in cancer cells leads to both the transcription of key tumor-promoting genes and cancer cell proliferation.

• Audencel - A therapeutic interleukin-12 (IL-12)-expressing dendritic cell (DC)-based vaccine composed of autologous monocyte-derived DCs loaded with autologous tumor cell lysate and exposed to the microbial cell wall component lipopolysaccharide (LPS), with potential immunomodulating and antineoplastic activities. The monocyte-derived immature DCs are loaded with autologous tumor cell lysates and are subsequently exposed to LPS and interferon-gamma (IFN-gamma). Upon administration of audencel, the mature DCs migrate into the lymph nodes, express the immune stimulatory cytokine interleukin-12 (IL-12) and activate the immune system by promoting the activation of natural killer (NK) cells and induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. Exposure to LPS and IFN-gamma allows the maturation of DCs and optimizes the presentation of tumor-associated antigens (TAAs) by DCs to T-lymphocytes.

• Auranofin - An orally available, lipophilic, organogold compound, used to treat rheumatoid arthritis, with anti-inflammatory and potential antineoplastic activities. Auranofin interacts with selenocysteine residue within the redox-active domain of mitochondrial thioredoxin reductase (TrxR), thereby blocking the activity of TrxR. As a result, this agent induces mitochondrial oxidative stress leading to the induction of apoptosis. Furthermore, this agent strongly inhibits the JAK1/STAT3 signal transduction pathway, thereby suppressing expression of immune factors involved in inflammation. TrxR, overexpressed in many cancer cell types, inhibits apoptosis, promotes cell growth and survival and plays a role in resistance to chemotherapy; TrxR catalyzes the reduction of oxidized thioredoxin (Trx) and plays a central role in regulating cellular redox homeostasis.

• Aurora a kinase inhibitor ly3295668 - An orally bioavailable inhibitor of the serine/threonine protein kinase aurora A, with potential antimitotic and antineoplastic activities. Upon administration, aurora A kinase inhibitor LY3295668 targets, binds to and inhibits the activity of aurora A kinase. This may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing aurora A kinase. Aurora A kinase, overexpressed in a wide variety of cancers, plays an essential role in the regulation of spindle assembly and mitosis.

• Aurora a kinase inhibitor ly3295668 erbumine - The tert-butylamine salt form of LY3295668, an orally bioavailable inhibitor of the serine/threonine protein kinase aurora A, with potential antimitotic and antineoplastic activities. Upon administration, aurora A kinase inhibitor LY3295668 targets, binds to and inhibits the activity of aurora A kinase. This may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing aurora A kinase. Aurora A kinase, overexpressed in a wide variety of cancers, plays an essential role in the regulation of spindle assembly and mitosis.

• Aurora a kinase inhibitor mk5108 - An orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A, with potential antimitotic and antineoplastic activity. Aurora A kinase inhibitor MK5108 binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and eventually inhibition of cell division, proliferation and an induction of apoptosis in cells overexpressing Aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis, and is thought to regulate spindle assembly. Aurora kinases are overexpressed in a wide variety of cancers.

• Aurora a kinase inhibitor tas-119 - An orally bioavailable inhibitor of the serine/threonine protein kinase aurora A, with potential antimitotic and antineoplastic activities. Upon intravenous administration, aurora A kinase inhibitor TAS-119 binds to and inhibits aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis; it plays an essential role in the regulation of spindle assembly. Aurora kinase A is overexpressed in a wide variety of cancers.

• Aurora a kinase/tyrosine kinase inhibitor enmd-2076 - An orally bioavailable synthetic small molecule with potential antiangiogenic and antineoplastic activities. Aurora A kinase/tyrosine kinase inhibitor ENMD-2076 selectively binds to and inhibits non-specified tyrosine kinases and Aurora kinases (AKs). The inhibition of AKs may result in the inhibition of cell division and proliferation and may induce apoptosis in tumor cells that overexpress AKs; antiangiogenic activity is related to the inhibition of angiogenic tyrosine kinases. AKs are serine-threonine kinases that play an essential role in mitotic checkpoint control during mitosis and are important regulators of cell division and proliferation.

• Aurora b serine/threonine kinase inhibitor tak-901 - A small-molecule inhibitor of the serine-threonine kinase Aurora B with potential antineoplastic activity. Aurora B kinase inhibitor TAK-901 binds to and inhibits the activity of Aurora B, which may result in a decrease in the proliferation of tumor cells that overexpress Aurora B. Aurora B is a positive regulator of mitosis that functions in the attachment of the mitotic spindle to the centromere; the segregation of sister chromatids to each daughter cell; and the separation of daughter cells during cytokinesis. This serine/threonine kinase may be amplified and overexpressed by a variety of cancer cell types.

• Aurora b/c kinase inhibitor gsk1070916a - An ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor GSK1070916A binds to and inhibits the activity of Aurora B and C, which may result in inhibition of cellular division and a decrease in the proliferation of tumor cells that overexpress the Aurora kinases B and C. Aurora kinases play essential roles in mitotic checkpoint control during mitosis, and are overexpressed by a wide variety of cancer cell types.

• Aurora kinase a/b inhibitor tt-00420 - An orally available small molecule inhibitor of Aurora kinases (AKs) A and B and other currently undisclosed kinases with potential antineoplastic and immunomodulatory activities. Upon oral administration, Aurora kinase inhibitor TT-00420 selectively binds to and inhibits AKs A and B, which may inhibit cell division in tumor cells that overexpress AKs. TT-00420 may also target other not yet disclosed kinases that play a role in tumor-associated inflammation and immune evasion. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of cancer cell types.

• Aurora kinase inhibitor amg 900 - A small-molecule inhibitor of Aurora kinases A, B and C with potential antineoplastic activity. Aurora kinase inhibitor AMG 900 selectively binds to and inhibits the activities of Aurora kinases A, B and C, which may result in inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis and are overexpressed by a wide variety of cancer cell types.

• Aurora kinase inhibitor bi 811283 - A small molecule inhibitor of the serine/threonine protein kinase Aurora kinase with potential antineoplastic activity. Aurora kinase inhibitor BI 811283 binds to and inhibits Aurora kinases, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation.

• Aurora kinase inhibitor mln8054 - An orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Auora kinase inhibitor MLN8054 binds to and inhibits Aurora kinase A, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. Aurora A localizes in mitosis to the spindle poles and to spindle microtubules and is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers.

• Aurora kinase inhibitor pf-03814735 - An aurora kinase inhibitor with potential antineoplastic activity. PF-03814735 binds to and inhibits aurora kinases, serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis. Inhibition of aurora kinases may result in an inhibition of cellular division and proliferation in tumor cells that overexpress aurora kinases.

• Aurora kinase inhibitor sns-314 - A synthetic small molecule Aurora kinase (AK) inhibitor with potential antineoplastic activity. Aurora kinase inhibitor SNS-314 selectively binds to and inhibits AKs A and B, which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress AKs. AKs are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis.

• Aurora kinase inhibitor ttp607 - A small-molecule pan-Aurora kinase inhibitor with potential antineoplastic activity. Aurora kinase inhibitor TTP607 selectively binds to and inhibits Aurora kinases A, B and C, which may result in the disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cellular division and proliferation in Aurora kinase-overexpressing tumor cells. Aurora kinases A, B and C, are serine/threonine kinases that play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types.

• Aurora kinase/vegfr2 inhibitor cyc116 - An orally bioavailable small molecule multi-kinase inhibitor with antineoplastic activity. Aurora kinase/VEGFR 2 inhibitor CYC116 inhibits Aurora kinases A and B and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in disruption of the cell cycle, rapid cell death, and the inhibition of angiogenesis. Aurora kinases are serine/threonine protein kinases that are only expressed in actively dividing cells and are critical in division or mitosis. VEGFR2 is a receptor tyrosine kinase that appears to account for most of the mitogenic and chemotactic effects of vascular endothelial growth factor (VEGF) on adult endothelial cells.

• Autologous 4-1bb selected tumor infiltrating lymphocytes - A preparation of autologous tumor infiltrating lymphocytes (TILs) expressing the co-stimulatory signaling domain 4-1BB (CD137), with potential antineoplastic activity. TILs are isolated from a patient's tumor and those expressing 4-1BB are selected for expansion in vitro. Upon re-infusion into the patient, the 4-1BB-expressing TILs re-infiltrate the tumor to initiate tumor cell lysis. 4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, enhances TIL survival and antitumor cytolytic activity.

• Autologous active il-7 receptor co-expressing gd2-specific car t-cells - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) GD2, and the constitutively active interleukin 7 (IL-7) receptor (C7R), with potential antineoplastic activity. Upon intravenous administration, autologous active IL-7 receptor co-expressing GD2-specific CAR T-cells target, bind to, and induce selective toxicity in GD2-expressing tumor cells. C7R triggers IL-7-mediated signaling that promotes T-cell proliferation, survival, and anti-tumor activity. GD2, a disialoganglioside and TAA, is overexpressed in a variety of tumor cell types.

• Autologous actr-cd16-cd28-expressing t-lymphocytes actr707 - A preparation of autologous T-lymphocytes that have been genetically modified, using proprietary Antibody-Coupled T-cell Receptor (ACTR) technology, to express a chimeric protein containing, at least, the extracellular Fc receptor domain of CD16, normally found on certain immune cells, such as natural killer (NK) cells, coupled to the co-stimulatory signaling domain of CD28, with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient with co-administration of a cancer-specific antibody, the co-administered antibody targets and binds to the tumor-associated antigen (TAA) expressed on the tumor cell. In turn, the autologous ACTR-CD16-CD28-expressing T-lymphocytes ACTR707 bind to the antibody, become activated and induce the destruction of the tumor cells by a) releasing cytotoxins that directly kill cancer cells; b) releasing cytokines that trigger an immune response and recruit other immune-mediated killer cells to kill the tumor cells; c) targeting and killing adjacent tumor cells that are not bound to the antibody; d) inducing T-cell proliferation and thereby further enhancing the T-cell mediated tumor cell attack. Compared to other T-cell products, ACTR-based products do not target a specific TAA and can potentially be used in a variety of tumors because targeting is based on the specificity of the co-administered antibody.

• Autologous ad-cd154-transduced cll b cells - An autologous tumor cell vaccine containing chronic lymphocytic leukemia (CLL) B cells transduced with an adenoviral vector carrying chimeric CD154 (ad-CD154) with potential antineoplastic activity. Administration of autologous ad-CD154 transduced CLL B cells may result in increases in the numbers of leukemia-specific CD4+ T cells and high serum-levels of IL-12 and IFN-gamma. Due to ligation of CD154 to CD40 on CLL cells, this agent may induce CLL cells to express the proapoptotic molecule BID and death receptors CD95 (Fas) and DR5, rendering CLL B cells first resistant and then sensitive to Fas-mediated apoptosis. In addition, autologous ad-CD154 transduced CLL B cells may induce MHC class I-dependent cytotoxic T lymphocyte (CTL) responses against autologous leukemia cells. CD154 is a type II membrane glycoprotein and ligand for CD40; both molecules are important in cognate co-stimulatory cell-cell interactions.

• Autologous afp specific t cell receptor transduced t cells c-tcr055 - A preparation of human autologous T-lymphocytes transduced with a lentiviral vector encoding for a T-cell receptor (TCR) recognizing the human leukocyte antigen (HLA)-A*02:01 restricted human alpha-fetoprotein (AFP) 158-166 peptide (FMNKFIYEI), with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the AFP specific TCR transduced T cells 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 while its expression is restricted in normal tissues.

• Autologous aml/dendritic cell fusion vaccine - A therapeutic cell-based cancer vaccine consisting of autologous dendritic cells (DCs) fused with autologous acute myeloid leukemia (AML) cells, with potential immunostimulatory and antineoplastic activities. The autologous AML/DC fusion vaccine is generated in vitro by mixing DCs and irradiated AML cells harvested from individual patients, in the presence of polyethylene glycol (PEG), to produce hybrid DC-leukemia fusion cells. Upon re-administration, the autologous AML/DC fusion vaccine may elicit a cytotoxic T-lymphocyte (CTL)-mediated antitumor immune response against a broad array of AML-associated antigens, which may lead to AML cell lysis.

• Autologous anti-b7-h3 car retroviral vector-transduced t cells - A preparation of autologous T-lymphocytes that have been transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) targeting the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and containing, as of yet undisclosed co-stimulatory signaling domains, with potential immunostimulating and antineoplastic activities. Upon infusion back into the patient, autologous anti-B7-H3 CAR retroviral vector-transduced T cells target and bind to B7-H3-expressing tumor cells, thereby inducing selective toxicity in B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of the T-cell activation and its overexpression plays a key role in tumor cell invasion and metastasis.

• Autologous anti-b7-h3/cd19 car t-cells scri-carb7h3(s)x19 - A preparation of autologous CD4+ and CD8+ T-lymphocytes lentivirally transduced to express a chimeric antigen receptor (CAR) targeting the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and the tumor-associated antigen (TAA) CD19, and containing, as of yet undisclosed co-stimulatory signaling domains, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon administration, anti-B7-H3/CD19 CAR T-cells target and bind to both B7-H3 on T-cells and CD19 on tumor cells. This crosslinks T-cells and tumor cells, and induces selective toxicity in B7-H3/CD19-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It promotes the activation of T cells. CD19, a transmembrane phosphoglycoprotein expressed on the surface of cells in the B lineage, are often overexpressed on malignant B-cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.

• Autologous anti-bcma car t-cells im21 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector (LV) expressing a chimeric antigen receptor (CAR) targeting the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) and containing, as of yet undisclosed costimulatory signaling domains, with potential antineoplastic activity. Upon administration, the autologous anti-BCMA CAR T-cells IM21 recognize and induce selective toxicity against BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma car t-cells phe885 - A preparation of autologous T-lymphocytes that have been genetically engineered to express a chimeric antigen receptor (CAR) targeting the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential antineoplastic activity. Upon administration, the autologous anti-BCMA CAR T-cells PHE885 recognize and induce selective toxicity against BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma car-transduced t-cells kite-585 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) containing a single chain variable fragment (scFv) derived from a human monoclonal antibody specific for the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) fused, via an as of yet unknown linker, to the co-stimulatory domain of CD28, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-BCMA CAR transduced T-cells KITE-585 specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF). BCMA is found on the surfaces of plasma cells, is overexpressed on malignant plasma cells and plays a key role in plasma cell proliferation and survival. The CD28 co-stimulatory domain optimizes T-cell expansion and function.

• Autologous anti-bcma cd8+ car t-cells descartes-11 - A preparation of autologous CD8-positive T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) human B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-BCMA CD8+ CAR T-cells Descartes-11 specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car expressing stem memory t-cells p-bcma-101 - A preparation consisting of autologous T-cells that are enriched to be primarily stem memory T-cells (Tscm) and are transfected by electroporation with a proprietary transposon-based DNA plasmid vector (PiggyBac) containing an undisclosed selection gene and encoding both an unidentified human-derived safety switch and a chimeric antigen receptor (CAR) based on a proprietary non-immunoglobulin scaffold molecule Centyrin (CARTyrin), which specifically recognizes human B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-BCMA-CAR-expressing Tscm P-BCMA-101 specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. Use of CARTyrin may elicit less immunotoxicity than agents based on antibody-derived single chain variable fragments (scFv), and this agent may exhibit increased persistence and decreased exhaustion for the administered T-cells. If significant side effects occur, the safety switch mechanism can induce the rapid attenuation or elimination of P-BCMA-101. BCMA, a tumor-specific antigen and a member of the tumor necrosis factor receptor superfamily (TNFRSF) that binds to both a proliferation-inducing ligand (APRIL; TNFSF13) and B-cell activating factor (BAFF; TNFSF13B), plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-4-1bb-cd3zeta-egfrt-expressing cd4+/cd8+ t-lymphocytes - A preparation of an approximately equal ratio of autologous CD4- and CD8-positive T-lymphocytes that have been ex vivo transduced with a genetically-engineered self-inactivating (SIN) lentiviral vector (LV) expressing a chimeric antigen receptor (CAR) containing a single chain variable fragment (scFv) specific for the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) fused to the co-stimulatory domain of 4-1BB (CD137), the CD3-zeta (CD3z) T-cell signaling domain, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-BCMA-CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes specifically recognize and induce selective toxicity against BCMA-expressing tumor cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt facilitates both in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-4-1bb-cd3zeta-expressing memory t-lymphocytes bb21217 - A preparation of autologous memory T-lymphocytes transduced, ex vivo, with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-B-cell maturation antigen (BCMA) single chain variable fragment (scFv) fused to the signaling domain of 4-1BB (CD137) and a CD3-zeta T-cell activation domain, with potential immunostimulating and antineoplastic activities. Upon intravenous administration back into the patient, the autologous anti-BCMA-CAR-4-1BB-CD3zeta-expressing memory T-lymphocytes bb21217 are directed to, and induce selective toxicity in, BCMA-expressing tumor cells. BCMA, a tumor specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma survival. BCMA is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-4-1bb-cd3zeta-expressing t-cells c-car088 - A preparation of autologous T-lymphocytes that have been transduced with a vector expressing a chimeric antigen receptor (CAR) containing a single chain variable fragment (scFv) specific for the epitome cluster E3 in the extracellular domain (ECD) of the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) that is fused to the co-stimulatory domain of 4-1BB (CD137) and the T-cell receptor signaling domain of CD3zeta (CD3z), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-BCMA-CAR-4-1BB-CD3zeta-expressing T-cells C-CAR088 specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in the survival of B-lymphocytes and plasma cells. BCMA is found on the surfaces of B-cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-4-1bb-cd3zeta-expressing t-cells ct053 - A preparation of autologous T-lymphocytes that have been transduced with a vector expressing a chimeric antigen receptor (CAR) containing a humanized single chain variable fragment (scFv) specific for the tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) that is fused to the co-stimulatory domain of 4-1BB (CD137) and the T-cell receptor signaling domain of CD3zeta (CD3z), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-BCMA-CAR-4-1BB-CD3zeta-expressing T-cells CT053 specifically recognize and induce selective toxicity against BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in the survival of B-lymphocytes and plasma cells. BCMA is found on the surfaces of B-cells and is overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-expressing cd4+/cd8+ t-lymphocytes fcarh143 - A preparation of ex vivo expanded autologous CD8+ and CD4+ T-cells that have been genetically modified to express a chimeric antigen receptor (CAR) specific for human B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143 specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a tumor specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor (TNF) receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-mrna-transfected cd8+ t-lymphocytes - A preparation of autologous CD8-positive T-lymphocytes that have been genetically modified via transient mRNA transfection to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) human B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) and containing, as of yet undisclosed co-stimulatory signaling domains, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-BCMA-CAR-mRNA transfected CD8+ T-lymphocytes specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and overexpressed on malignant plasma cells.

• Autologous anti-bcma-car-tcrz/4-1bb-expressing t-lymphocytes cart-bcma - A preparation of autologous T-lymphocytes that have been ex vivo transduced with a genetically-engineered lentiviral vector (LV) expressing a chimeric antigen receptor (CAR) containing an extracellular human single chain variable fragment (scFv) specific for the tumor-associated antigen (TAA) human B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) fused to an intracellular tandem signaling domain comprised of the co-stimulatory domain of 4-1BB (CD137) and the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3z), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-BCMA-CAR-4-1BB-CD3zeta-expressing T-lymphocytes specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in plasma cell survival. BCMA is found on the surfaces of plasma cells and overexpressed on malignant plasma cells.

• Autologous anti-cd123 car tcr/4-1bb-expressing t-lymphocytes - Autologous, genetically engineered T-lymphocytes that have been electroporated with a messenger RNA (mRNA) encoding a chimeric antigen receptor (CAR) consisting of an anti-human interleukin-3 receptor alpha chain (IL3RA; CD123) single chain variable fragment (scFv) coupled to the co-stimulatory signaling domains of 4-1BB (CD137) and the zeta chain of the T-cell receptor (TCR) CD3 complex (CD3-zeta), with potential immunomodulating and antineoplastic activities. Upon transfusion, the mRNA-electroporated autologous anti-CD123 CAR TCR/4-1BB expressing T-lymphocytes attach to cancer cells expressing CD123. This induces selective toxicity in and causes lysis of CD123-expressing tumor cells. The 4-1BB co-stimulatory molecule signaling domain enhances T-cell activation and signaling after recognition of CD123. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with both increased leukemic cell proliferation and aggressiveness.

• Autologous anti-cd123 car-t cells - A preparation of autologous T-cells engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD123 (interleukin-3 receptor alpha chain or IL3RA), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD123 CAR-T cells target and bind to CD123 expressed on the surface of tumor cells. This induces selective toxicity in CD123-expressing tumor cells. CD123, the alpha subunit of the IL-3 receptor, regulates the proliferation, survival and differentiation of hematopoietic cells. It is overexpressed on a variety of cancers, including myeloid leukemia, and the increased expression of CD123 on leukemic stem cells (LSCs) is associated with poor prognosis.

• Autologous anti-cd147 car t-cells - A preparation of autologous activated T cells that have been engineered to express chimeric antigen receptors (CARs) specific for the tumor-associated antigen (TAA) CD147 (Basigin; EMMPRIN; extracellular matrix metalloproteinase inducer; OX47; 5A11), with potential antineoplastic activity. Upon administration back into the patient, the anti-CD147 CAR T-cells target and induce selective cytotoxicity in CD147-expressing tumor cells. CD147, a cell-surface glycoprotein of the immunoglobulin G (IgG) superfamily, is overexpressed in certain human tumors and plays an important role in tumor cell proliferation, migration, progression, and metastasis.

• Autologous anti-cd19 car t-cells 19(t2)28z1xx - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, and linked to the co-stimulatory intracellular signaling domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta; CD28z), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD19 CAR T-cells 19(T2)28z1xx specifically recognize and bind to CD19-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies and normal B-cells. CD28 and CD3zeta provide co-stimulatory activity and may enhance the cytotoxic effect and anti-tumor activity of the CAR T-cells. The 19(T2)28z1xx CAR T-cells include a 1928zeta mutant, 1xx, which contains one instead of all three immunoreceptor tyrosine-based activation motifs (iTAMs). This may help prevent counterproductive T-cell differentiation and exhaustion.

• Autologous anti-cd19 car t-cells im19 - A preparation of autologous T-lymphocytes that have been genetically modified and transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and containing, as of yet undisclosed co-stimulatory signaling domains, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 CAR T-cells IM19 target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car tcr-zeta/4-1bb-transduced t-lymphocytes hucart19 - Autologous T-lymphocytes that have been transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) consisting of a humanized single chain variable fragment (scFv) of anti-CD19 coupled to the cytoplasmic portion of the zeta chain of the human T-cell receptor (CD3zeta) and the co-stimulatory molecule 4-1BB (CD137), with potential immunostimulating and antineoplastic activities. Upon re-introduction into the patient, the autologous anti-CD19 CAR TCR-zeta/4-1BB-transduced T-lymphocytes huCART19 target and bind to CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells, resulting in tumor cell lysis. CD19 (cluster of differentiation 19) is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. Incorporation of the co-stimulatory signaling domains increases human T-cell function, expansion, and survival.

• Autologous anti-cd19 car-4-1bb-cd3zeta-expressing t-cells cnct19 - A preparation of autologous T-lymphocytes that are engineered to express a chimeric antigen receptor (CAR) composed of an anti-cluster of differentiation 19 (CD19) single chain variable fragment (scFv) linked to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous anti-CD19 CAR-4-1BB-CD3zeta-expressing T-cells CNCT19 target, bind to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car-cd28 t-cells et019002 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) of anti-CD19, coupled to the costimulatory domain of CD28, with potential immunostimulating and antineoplastic activities. Upon transfusion, the autologous anti-CD19 CAR-CD28 T-cells ET019002 target, bind to, and induce selective toxicity in CD19-expressing B-cells. The CD19 antigen is a B-cell-specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car-cd3zeta-4-1bb-expressing t-cells - A preparation of autologous T-lymphocytes that are engineered to express a chimeric antigen receptor (CAR) composed of an anti-cluster of differentiation 19 (CD19) single chain variable fragment (scFv) linked to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential immunomodulating and antineoplastic activities. Upon administration of the autologous anti-CD19 CAR-CD3zeta-4-1BB-expressing T-cells, these cells target, bind to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car-cd3zeta-4-1bb-expressing t-cells pz01 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) of anti-CD19, coupled to the costimulatory domains of 4-1BB (CD137) and the zeta chain of the human T-cell receptor (CD3zeta), with potential immunostimulating and antineoplastic activities. Upon transfusion, the autologous anti-CD19 CAR-CD3zeta-4-1BB-expressing T-cells PZ01 target, bind to, and induce selective toxicity in CD19-expressing B cells. The CD19 antigen is a B-cell-specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car-expressing t lymphocytes - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) that targets the human tumor associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 CAR-expressing T lymphocytes bind to and induce selective toxicity against CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 car-expressing t-lymphocytes clic-1901 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) that targets the human tumor associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 CAR-expressing T-lymphocytes CLIC-1901 bind to and induce selective toxicity against CD19-expressing tumor cells. The CD19 antigen is a B-cell-specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 chimeric antigen receptor t-cells auto1 - A preparation of autologous T-lymphocytes that have been genetically modified and transduced with a lentiviral vector expressing a second-generation chimeric antigen receptor (CAR), CAT-41BBz CAR, targeting the tumor-associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 CAR T-cells AUTO1 target and bind to CD19-expressing tumor cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and tumor cell lysis. CD19, cluster of differentiation 19, is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. The CAT-41BBz CAR has a faster off-rate compared with FMC63-41BBz CAR. This may minimize cytokine release and reduce toxicities, and enhance persistence of the CAR T-cells.

• Autologous anti-cd19 chimeric antigen receptor t-cells sjcar19 - A proprietary preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and containing, as of yet undisclosed, costimulatory signaling domains, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 CAR T-cells SJCAR19 target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous anti-cd19 tac-t cells tac01-cd19 - A preparation of autologous T-lymphocytes genetically engineered with a T cell Antigen Coupler (TAC), comprising of a domain that targets the tumor-associated antigen (TAA) cluster of differentiation 19 (CD 19) and another domain that binds to the endogenous T cell receptor (TCR), anchored in the membrane via the CD4 co-receptor domain, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-CD19 TAC-T cells TAC01-CD19 targets and binds to CD19-expressing tumor cells and activates TCR-mediated signaling pathways, leading to T cell-mediated killing of CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies.

• Autologous anti-cd19 t-cell receptor fusion construct t-cells tc-110 - A preparation of autologous T-lymphocytes that have been genetically engineered to express a single-domain antibody that recognizes human CD19, fused to the CD3-epsilon T-cell receptor (TCR) subunit which, upon expression is incorporated into the endogenous TCR complex, with potential antineoplastic activity. Upon administration, the autologous anti-CD19 TCR fusion construct (TRuC) T-cells TC-110 specifically target and bind to CD19-expressing tumor cells. This leads to T-cell activation and T-cell mediated lysis of CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies. Compared to chimeric antigen receptor (CAR) T-cells, TRuCs may be associated with less pro-inflammatory cytokine secretion and fewer adverse effects without compromising therapeutic efficacy.

• Autologous anti-cd19 t-cell receptor t cells et190l1 - Autologous human peripheral blood T-lymphocytes transduced with a lentivirus encoding a proprietary expression construct composed of a T-cell receptor (TCR)-like human antibody, which is synthesized by a proprietary phage display platform, targeting peptides derived from the tumor-associated antigen (TAA) CD19 that are presented in the context of major histocompatibility complex (MHC) molecules, with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and re-introduction into the patient, the autologous anti-CD19 TCR T-cells ET190L1 target and bind to tumor cells expressing CD19 peptide/MHC complexes. This results in cytotoxic T-lymphocyte (CTL)-mediated elimination of CD19-positive tumor cells. CD19, cluster of differentiation antigen 19, is a B-cell-specific cell surface antigen overexpressed in B-cell lineage malignancies. ET190L1 is able to match the anticancer activity of chimeric antigen receptor (CAR) T-cells; however, ET190L1 is less likely to stimulate cytokine release syndrome (CRS) and does not cause CAR T-cell-triggered neurotoxicity.

• Autologous anti-cd19/anti-cd20-car-cd28-4-1bb-cd3zeta-egfrt+-expressing tn/mem cells - A preparation of genetically modified autologous naive/memory T-cells (Tn/mem), that have been transduced with a self-inactivating (SIN) lentiviral vector to express a bispecific chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) of anti-CD19, derived from the anti-CD19 monoclonal antibody FMC63, in tandem with an anti-CD20 scFv, derived from the anti-CD20 monoclonal antibody Leu16, and fused to the hinge domain of human immunoglobulin (Ig) G4, the transmembrane domain of human CD28, and the cytoplasmic signaling domains of 4-1BB (CD137) and the T-cell antigen receptor complex zeta chain (CD3-zeta) (BBz), and linked via the T2A sequence to a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon transfusion, autologous anti-CD19/anti-CD20-CAR-CD28-4-1BB-CD3zeta-EGFR+-expressing Tn/mem cells recognize and induce selective toxicity in CD19/CD20-expressing tumor cells, resulting in tumor cell lysis. Both CD19 and CD20 are B-cell-specific cell surface antigens overexpressed in B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered T-cells and can promote elimination of those cells upon a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.

• Autologous anti-cd19/cd20 bispecific nanobody-based car-t cells - A preparation of autologous T-lymphocytes engineered to express a chimeric antigen receptor (CAR) that is nanobody-based and specific for the two tumor-associated antigens (TAAs) cluster of differentiation 19 (CD19) and CD20, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD19/CD20 bispecific nanobody-based CAR-T cells target and bind to CD19- and CD20-expressing tumor B-cells. This induces selective toxicity in tumor B-cells expressing these TAAs. Both CD19 and CD20 are B-cell-specific cell surface antigens overexpressed in B-cell lineage malignancies. Targeting both CD19 and CD20 may prevent tumor cell antigen escape and relapse.

• Autologous anti-cd19/cd22 car t-cells auto3 - A preparation of autologous T-lymphocytes that have been transduced with a bicistronic retroviral vector encoding both an anti-CD19 chimeric antigen receptor (CAR) fused to OX40 co-stimulatory domain and an anti-CD22 CAR linked to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), optimized with a novel pentameric spacer derived from the collagen oligomeric matrix protein (COMP), with potential antineoplastic activity. Upon administration, the autologous anti-CD19/CD22 CAR T-cells AUTO3 bind to and induce selectivity in tumor cells expressing CD19 and CD22. CD19 and CD22, both transmembrane phosphoglycoproteins expressed on the surface of cells in the B lineage, are often overexpressed on malignant B-cells. By simultaneously targeting two B-cell antigens, this preparation may minimize relapse due to single antigen loss in patients with B-cell malignancies.

• Autologous anti-cd19car-4-1bb/cd3zeta-her2tg-expressing cd4+/cd8+ t-lymphocytes scri-hucar19v2 - A preparation of autologous CD4- and CD8-positive T-lymphocytes that have been transduced with a lentiviral vector (LV) expressing a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) CD19 that is fused to the intracellular cytoplasmic domain of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (CD3zeta), and linked to a truncated form of the human epidermal growth factor receptor 2 (HER2tG), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD19CAR-4-1BB/CD3zeta-HER2tG-expressing CD4+/CD8+ T-lymphocytes SCRI-huCAR19v2 specifically target and bind to CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and causes tumor cell lysis. CD19 is a B-cell-specific cell surface antigen that is overexpressed in B-cell lineage tumors. Incorporation of the costimulatory signaling domain increases human T-cell function, expansion, and survival. Devoid of both ligand binding domains and tyrosine kinase activity, the co-expressed HER2tG both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a trastuzumab-induced antibody dependent cellular cytotoxicity (ADCC) response.

• Autologous anti-cd19car-4-1bb-cd3zeta-egfrt-expressing cd4+/cd8+ central memory t-lymphocytes jcar014 - A defined preparation of CD4+ and CD8+ central memory (CM) autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) fused to the signaling domains of CD28, 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+CM T-lymphocytes JCAR014 are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response. The 4-1BB costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity.

• Autologous anti-cd19car-4-1bb-cd3zeta-egfrt-expressing t lymphocytes - A preparation of genetically modified CD8+ central memory (Tcm) and CD4+ autologous T-lymphocytes (1:1) transduced with a replication incompetent, self-inactivating (SIN) lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) derived from the murine IgG1 monoclonal antibody (mAb) FMC63, fused to the signaling domain of 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T lymphocytes are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity response. The 4-1BB costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity.

• Autologous anti-cd19car-cd28tm/4-1bb/cd3zeta-her2tg-expressing cd4+/cd8+ t-lymphocytes scri-hucar19v1 - A preparation of autologous CD4- and CD8-positive T-lymphocytes that have been transduced with a third-generation self-inactivating (SIN) lentiviral vector (LV) expressing a human-derived immunoglobulin G4 (IgG4) hinge-optimized chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) specific for CD19 that is fused to a human CD28 transmembrane domain (CD28tm), the intracellular cytoplasmic domain of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (CD3zeta), and linked to a truncated form of the human epidermal growth factor receptor 2 (HER2tG), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous CD4+/CD8+ T-lymphocytes SCRI-huCAR19v1 specifically target and bind to CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and causes tumor cell lysis. CD19 is a B-cell-specific cell surface antigen that is overexpressed in B-cell lineage tumors. Incorporation of the costimulatory signaling domains of CD28 and 4-1BB increases human T-cell function, expansion, and survival. Devoid of both ligand binding domains and tyrosine kinase activity, the co-expressed HER2tG both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a trastuzumab-induced antibody dependent cellular cytotoxicity (ADCC) response.

• Autologous anti-cd19car-cd3zeta-4-1bb-il-15-pd1-expressing tri-functional t-lymphocytes - A preparation of autologous T-lymphocytes engineered to express a tri-functional chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19), and an extracellular domain consisting of interleukin 15 (IL-15) and programmed cell death 1 (PD1; PDCD1; CD279; programmed death-1), linked to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential antineoplastic activity. Upon intravenous administration, autologous anti-CD19CAR-CD3zeta-4-1BB-IL-15-PD1-expressing tri-functional T-lymphocytes target, bind to, and induce selective toxicity in CD19-expressing tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and potentiates the immune response against tumor cells. The PD1 moiety binds to programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) on tumor cells, reversing T-cell inactivation caused by endogenous PD1/PD-L1 signaling and enhancing the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. Incorporation of the costimulatory signaling domains increases human T-cell function, expansion, and survival.

• Autologous anti-cd19car-her2t/cd22car-egfrt-expressing t-cells - A preparation of autologous human T-lymphocytes engineered to express dual chimeric antigen receptors (CARs) consisting of both anti-CD19 and anti-CD22 binding domains, fused to an as of yet undisclosed co-stimulatory domain, and linked to truncated forms of the human epidermal growth factor receptor 2 (HER2t) and the human epidermal growth factor receptor (EGFRt), respectively with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD19CAR-HER2t/CD22CAR-EGFRt-expressing T-cells bind to CD19 and CD22 on the surface of, and induce selective toxicity against tumor cells expressing CD19 and CD22. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt and HER2t facilitate both in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through an antibody-dependent cellular cytotoxicity (ADCC) response. CD19 and CD22, both transmembrane phosphoglycoproteins expressed on the surface of cells in the B lineage, are often overexpressed on malignant B-cells.

• Autologous anti-cd20 car transduced cd4/cd8 enriched t-cells mb-cart20.1 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD20 (cluster of differentiation 20), and CD4/CD8 enriched, with potential immunostimulating and antineoplastic activities. Upon administration, MB-CART20.1 specifically recognize and kill CD20-expressing tumor cells. The CD20 antigen, a non-glycosylated cell surface phosphoprotein, is a B-cell specific cell surface antigen expressed in B-cell lineage malignancies and certain melanoma cell subpopulations.

• Autologous anti-cd22 car-4-1bb-tcrz-transduced t-lymphocytes cart22-65s - Autologous human T-lymphocytes transduced with a recombinant lentiviral vector encoding a chimeric antigen receptor (CAR) consisting of an anti-CD22 human single chain variable fragment (scFv) and linked to the co-stimulatory domain 4-1BB (CD137) coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta), with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient, the autologous anti-CD22 CAR-4-1BB-TCRz -transduced T-lymphocytes CART22-65s express anti-CD22-CAR on their cell surfaces and bind to the CD22 antigen on tumor cell surfaces, resulting in lysis of CD22-expressing tumor cells. CD22, a B-lineage-restricted, transmembrane phosphoglycoprotein, is expressed on malignant B-cells.

• Autologous anti-cd38 a2 car2-expressing t-cells - A preparation of genetically modified autologous T-cells expressing a chimeric antigen receptor recognizing the tumor-associated antigen (TAA) cluster of differentiation 38 (CD38), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous anti-CD38 A2 CAR2-expressing T-cells are directed to and induce selective toxicity in CD38-expressing tumor cells. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies, and its expression has been correlated with poor prognosis.

• Autologous anti-cd7 car/28zeta crispr-edited t-lymphocytes - A preparation of autologous T-lymphocytes (ATL) that have been gene-edited with the clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9 (Casp9) to remove the CD7 antigen and genetically engineered to express a chimeric antigen receptor (CAR) composed of a single-chain variable fragment (scFv) directed against the CD7 antigen and linked to the co-stimulatory domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-CD7 CAR/28zeta CRISPR-edited T-lymphocytes specifically recognize and bind to CD7-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD7 is a transmembrane glycoprotein expressed by T-cells and natural killer (NK) cells and their precursors. It is expressed in the majority of lymphoblastic T-cell leukemias and lymphomas and in a subset of peripheral T-cell lymphomas. Removal of the endogenous CD7 antigen from the T-cell surface increases expansion and viability of the CAR-T cells and increases T-cell cytotoxic activity.

• Autologous anti-cs1 hinge-optimized car-4-1bb-egfrt-expressing memory-enriched t-cells - A preparation of autologous central memory-enriched T-cells (Tcm) that have been transduced with a self-inactivating (SIN) lentiviral vector expressing a hinge-optimized chimeric antigen receptor (CAR) comprised of a CS1 (CD2 subset 1; SLAM family member 7; SLAMF7; CD319; CRACC)-specific single chain variable fragment (scFV), fused to the costimulatory signaling domain of 4-1BB (CD137), and a truncated human epidermal growth factor receptor (huEGFRt), with potential antineoplastic activity. Upon intravenous infusion, anti-CS1-CAR-4-1BB-CD3z-EGFRt-expressing Tcm-enriched T-lymphocytes target and induce selective toxicity in CS-1-expressing tumor cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed huEGFRt facilitates both in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. CS1, a cell surface glycoprotein of the signaling lymphocyte activation molecule (SLAM) receptor family, is highly expressed on certain malignant plasma cells.

• Autologous anti-egfr car-transduced cxcr 5-modified t-lymphocytes - A preparation of autologous, C-X-C chemokine receptor type 5 (CXCR 5)-modified T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the epidermal growth factor receptor (EGFR), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-EGFR CAR-transduced CXCR 5-modified T-lymphocytes target and bind to EGFR-expressing tumor cells, thereby inducing selective toxicity in EGFR-expressing tumor cells. EGFR, overexpressed by a variety of cancer cell types, plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance. CXCR5, and its ligand C-X-C motif chemokine 13 (CXCL13), are associated with a variety of tumors. CXCR5-CXCL13 interactions may be involved in the regulation of lymphocyte infiltration within the tumor microenvironment (TME).

• Autologous anti-egfrviii 4scar-igt cells - A preparation of autologous T-cells that are genetically modified to express immunoglobulins (Igs) that target the negative immunoregulatory human cell surface receptor programmed cell death protein 1 (PD-1; PDCD1; CD279) and programmed death-ligand 1 (PD-L1; CD274) and are transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of a single chain variable fragment (scFv) targeting anti-epidermal growth factor receptor variant III (EGFRvIII) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-EGFRvIII 4SCAR-IgT cells are directed to and induce selective toxicity in EGFRvIII-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. EGFRvIII, a tumor-associated antigen (TAA) encoded by an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types and is not expressed by normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity. The anti-PD-1 and anti-PD-L1 antibodies produced by the T-cells (IgT) bind to PD-1, expressed on T-cells, and its ligand PD-L1 expressed on cancer cells, respectively. This inhibits PD-1/PD-L1-mediated signaling, prevents T-cell inhibition and exhaustion, enhances T-cell activation within the tumor microenvironment (TME) and results in an enhanced T-cell-mediated immune response against and toxicity in the EGFRvIII-expressing tumor cells.

• Autologous anti-flt3 car t cells amg 553 - A preparation of autologous T-lymphocytes genetically engineered with a chimeric antigen receptor (CAR) specific for the tumor-associated antigen FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2), with potential immunostimulating and antineoplastic activities. Upon administration, the anti-FLT3 CAR T cells AMG 553 target and bind to tumor cells expressing FLT3, which results in the cytotoxic T-lymphocyte (CTL)-mediated cell killing of FLT3-expressing tumor cells. FLT3, a class III receptor tyrosine kinase (RTK), is overexpressed or mutated in most B-lineage neoplasms and in acute myeloid leukemias (AMLs).

• Autologous anti-gd2-car-bbz-icasp9 retroviral vector-transduced t lymphocytes - A preparation of genetically modified autologous T-lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) derived from the monoclonal antibody 14g2a that is specific for the disialoganglioside GD2 and the co-stimulatory domain 4-1BB (CD137) coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta), and fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunomodulating and antineoplastic activities. Upon intravenous administration of the autologous anti-GD2-CAR-BBz-iCasp9 retroviral vector-transduced T lymphocytes, these cells target the GD2 antigen on tumor cells, thereby providing selective toxicity towards GD2-expressing tumor cells. The tumor-associated antigen (TAA) GD2 is overexpressed on the surface of neuroblastoma cells and by other neuroectoderm-derived neoplasms, while it is minimally expressed on normal cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered; this binds to the drug binding FKBP12-F36V domain and activates caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent.

• Autologous anti-gd2car-cd28-cd3zeta-il-15-expressing natural killer t-cells - A preparation of autologous natural killer T-lymphocytes (NKTs) that have been transduced with a retroviral vector to express both an extracellular domain consisting of interleukin 15 (IL-15) and a chimeric antigen receptor (CAR) specific for the human tumor associated antigen (TAA) GD2, linked to the CD28 and CD3zeta (TCRzeta; CD247) costimulatory signaling domains, with potential antineoplastic activity. Upon intravenous administration, autologous anti-GD2CAR-CD28-CD3zeta-IL-15-expressing NKTs target, bind to, and induce selective toxicity in GD2-expressing tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and potentiates the immune response against tumor cells. Incorporation of the costimulatory signaling domains increases T-cell function, expansion, and survival. The CD28 costimulatory molecule signaling domain enhances activation and signaling after recognition of GD2. Additionally, inclusion of the CD28 signaling domain may increase proliferation of T-cells and antitumor activity compared to the inclusion of the CD3zeta chain alone. GD2, a disialoganglioside and tumor-associated antigen (TAA), is overexpressed in a variety of tumor cell types.

• Autologous anti-gp100:154-162 t-cell receptor gene-engineered peripheral blood lymphocytes - Human autologous peripheral blood lymphocytes (PBLs) transduced with a glycoprotein 100 (gp100) epitope-determined T cell receptor (TCR) gene, with potential antineoplastic activity. PBLs are isolated from a melanoma patient and pulsed with a viral vector encoding the TCR specific for amino acid residues 154-162 of gp100 (KTWGQYWQV). After expansion ex vivo, the transduced autologous PBLs, expressing this specific TCR, are reintroduced into the patient and bind to melanoma cells expressing the gp100 protein, which may result in specific cytotoxic T-lymphocyte (CTL) killing of gp100-expressing melanoma cells. gp100 is a melanocyte lineage-specific antigen overexpressed in melanomas.

• Autologous anti-gp100car-cd3zeta-4-1bb-il-15-pd1-expressing tri-functional t-lymphocytes - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector encoding a tri-functional chimeric antigen receptor (TriCAR) comprised of an extracellular domain consisting of an antigen binding domain specific to glycoprotein 100 (gp100) peptides 209-217 complexed with human leukocyte antigen A2 (HLA-A2), interleukin 15 (IL-15) and programmed cell death 1 (PD1; PDCD1; CD279; programmed death-1), which are linked by a transmembrane domain to the intracellular signaling domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential antineoplastic activity. Upon administration, the autologous anti-gp100CAR-CD3zeta-4-1BB-IL-15-PD1-expressing tri-functional T-lymphocytes selectively bind to gp100 peptides presented by HLA-A2. Upon binding to the gp100-HLA complex, the T-cells release cytokines and induce selective toxicity in gp100-expressing tumor cells. IL-15 is a pro-survival cytokine that promotes T-cell persistence and potentiates the immune response against tumor cells. The PD1 moiety binds to programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) on tumor cells, reversing T-cell inactivation caused by endogenous PD1/PD-L1 signaling and enhancing the cytotoxic T-lymphocyte (CTL)-mediated anti-tumor immune response against PD-L1-expressing tumor cells.

• Autologous anti-her2-car-4-1bb-cd3zeta-cd19t+-expressing tcm-enriched t-lymphocytes - A preparation of genetically modified autologous central memory (Tcm) enriched T-cells transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-human epidermal growth factor 2 (HER2) single chain variable fragment (scFv) derived from trastuzumab, with a 4-1BB (CD137) costimulatory domain that is linked to the signaling domain of the T-cell antigen receptor complex zeta chain (CD3-zeta) (BBz), and truncated CD19 (CD19t), with potential immunostimulatory and antineoplastic activities. Upon intravenous infusion, Anti-HER2-CAR-4-1BB-CD19t+-expressing Tcm-enriched T-lymphocytes are directed against HER2-expressing cells, thereby inducing selective toxicity in HER2-expressing tumor cells. HER2, a receptor tyrosine kinase, is mutated or overexpressed in many tumor cell types, plays a significant role in tumor cell proliferation and tumor vascularization. The BBz costimulatory signaling domain enhances proliferation of T-cells and antitumor activity, while CD19t, a marker for transduction, is utilized to calculate CAR T-cell dosing and for CAR-expressing cell tracking. Tcm cells have the capacity for long-lived persistence and retain their ability to proliferate upon antigen re-encounter. The immunoglobulin G4 (IgG4) extracellular spacer contains a double mutation, (L235E;N297Q) (EQ) within the CH2 region to reduce Fc receptor recognition.

• Autologous anti-hla-a*02/afp tcrm-expressing t-cells et140202 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector to express a T-cell receptor mimetic (TCRm) antibody synthesized by a proprietary phage display platform, targeting the immunogenetic human tumor-associated antigen (TAA) alpha-fetoprotein (AFP) complexed with human leukocyte antigen (HLA)-A*02 (HLA-A*02/AFP), with potential antineoplastic and immunomodulatory activities. Upon administration, the autologous anti-HLA-A*02/AFP TCRm-expressing T-cells ET140202 specifically recognize and selectively bind to AFP peptides presented by HLA-A*02. This results in cytotoxic T-lymphocyte (CTL)-mediated elimination of AFP-expressing tumor cells. AFP, an intracellularly expressed fetal glycoprotein rarely expressed in adult tissues, is overexpressed in certain tumors of endodermal origin and plays a key role in tumor cell proliferation and survival. AFP is processed into peptides and presented by class I major histocompatibility complexes (MHCs) on the surface of tumor cells.

• Autologous anti-hla-a*0201/afp car t-cells et1402l1 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) containing a single chain variable fragment (scFv) derived from a human monoclonal antibody specific for an immunogenic human tumor-associated antigen (TAA) alpha-fetoprotein (AFP) epitope, AFP158-166, complexed with human leukocyte antigen (HLA)-A*02:01 (HLA-A*0201/AFP), fused to the co-stimulatory domains of CD28 and CD3zeta, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-HLA-A*0201/AFP CAR T-cells ET1402L1 specifically recognize and selectively bind to the AFP158-166 peptide presented by HLA-A*0201. Upon binding to the AFP-MHC complex, the T-cells release cytokines and induce selective toxicity in HLA-A*0201/AFP-positive tumor cells. AFP, an intracellularly expressed fetal glycoprotein rarely expressed in adult tissues, is overexpressed in certain tumors of endodermal origin and plays a key role in tumor cell proliferation and survival. AFP is processed into peptides and presented by class I major histocompatibility complexes (MHCs) on the surface of tumor cells.

• Autologous anti-hpv-16 e6 t-cell receptor gene-engineered peripheral blood lymphocytes - Human autologous peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding a T cell receptor (TCR) that is specifically directed against the viral oncoprotein human papillomavirus type 16 (HPV-16) E6, with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous anti-HPV-16 E6 TCR gene-engineered PBLs bind to HPV-16 E6-expressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of HPV-16 E6-positive cancer cells. HPV-16 E6, a cell surface glycoprotein, is overexpressed by a variety of HPV-associated cancers and is absent from healthy human tissues.

• Autologous anti-icam-1-car-cd28-4-1bb-cd3zeta-expressing t-cells aic100 - A preparation of autologous T-lymphocytes that have been transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) containing the Inserted (I) domain variant of lymphocyte function-associated antigen-1 (LFA-1) which targets intercellular adhesion molecule-1 (ICAM-1 or CD54), and the co-stimulatory signaling domains of CD28, 4-1BB (CD137) and CD3zeta, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-ICAM-1-CAR-CD28-4-1BB-CD3zeta-expressing T-cells AIC100 recognize and kill ICAM-1-expressing tumor cells. ICAM-1, normally expressed on leukocytes and endothelial cells, may be overexpressed in a variety of cancers. CAR T-cells AIC100 are also engineered to express somatostatin receptor subtype 2 (SSTR2), allowing the imaging of the CAR T-cells in patients.

• Autologous anti-kappa light chain car-cd28-expressing t-lymphocytes - A preparation of autologous T-lymphocytes (ATL) that have been genetically modified to express a chimeric antigen receptor (CAR) directed against the kappa light chain of immunoglobulin (Ig) and linked to the costimulatory domain of CD28, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous anti-kappa light chain CAR-CD28-expressing T-lymphocytes target and bind to the kappa light chain of Ig expressed on tumor cells, resulting in T-cell-mediated tumor cell lysis. In some B-cell malignancies, the expression of the Ig light chain kappa may be increased compared to the expression of Ig light chain lambda.

• Autologous anti-mart-1 f5 t-cell receptor gene-engineered peripheral blood lymphocytes - Human autologous peripheral blood lymphocytes (PBLs) transduced with a melanoma antigen MART-1 epitope-determined T cell receptor (TCR) gene, with potential antineoplastic activity. PBLs are isolated from a melanoma patient and pulsed with a viral vector that encodes the TCR specific for an epitope of MART-1 (F5 TCR). After expansion ex vivo, the transduced autologous PBLs, expressing this specific TCR, are reintroduced into the patient, and bind to melanoma cells expressing the MART-1 antigen, which may result in specific cytotoxic T-lymphocyte (CTL) killing of MART-1-expressing melanoma cells. MART-1 (melanoma antigen recognized by T cells 1), also known as Melan-A, is a melanocyte lineage-specific transmembrane protein.

• Autologous anti-mesothelin car-cd3zeta-4-1-bb-expressing t-cells - A preparation of autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-mesothelin M5 single chain variable fragment (scFv) fused to the costimulatory domains of 4-1BB (CD137) and the zeta chain of the TCR/CD3 complex (TCRzeta; CD247; CD3zeta), with potential immunomodulating and antineoplastic activities. After isolation, transduction, expansion in culture and reintroduction into the patient, the autologous anti-mesothelin CAR-CD3zeta-4-1BB-expressing T-cells specifically target and induce selective toxicity in mesothelin-expressing tumor cells. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types.

• Autologous anti-mesothelin t-cell receptor fusion construct t-cells tc-210 - A preparation of autologous T-lymphocytes that have been genetically engineered to express a single-domain antibody that recognizes human mesothelin, fused to the N-terminus of the CD3-epsilon T-cell receptor (TCR) subunit which, upon expression is incorporated into the endogenous TCR complex, with potential antineoplastic activity. Upon administration, the autologous anti-mesothelin TCR fusion construct (TRuC) T-cells TC-210 specifically target and bind to mesothelin-expressing tumor cells. This leads to T-cell activation and T-cell mediated lysis of mesothelin-expressing tumor cells. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. Compared to chimeric antigen receptor (CAR) T-cells, TRuCs may be associated with less pro-inflammatory cytokine secretion and fewer adverse effects without compromising therapeutic efficacy.

• Autologous anti-mg7-car t-lymphocytes - A preparation of autologous, engineered T-lymphocytes that express both a second-generation chimeric antigen receptor (CAR) specific for the human gastric carcinoma-associated antigen MG7, and the co-stimulatory molecule 4-1BB (CD137), with potential antineoplastic activity. Upon intratumoral injection, the autologous anti-MG7-CAR T-lymphocytes target and attach to cancer cells expressing MG7. This induces selective toxicity in and causes lysis of MG7-expressing tumor cells. MG7, a glycosylated protein sequence from the tumor-associated antigen (TAA) carcinoembryonic antigen (CEA), plays a key role in the development of certain tumor cell types. 4-1BB enhances T-cell activation and signaling after recognition of MG7.

• Autologous anti-muc1*-car-4-1bb-cd3zeta-expressing t-lymphocytes - A preparation of autologous T-lymphocytes transduced with a lentiviral vector encoding a human CD8 alpha leader sequence, a humanized MNC2-single chain variable fragment (scFv) targeting the extracellular domain of the cleaved form of mucin-1 (MUC-1), known as MUC1*, portions of human CD8 hinge and transmembrane domains, and human 4-1BB and human CD3-zeta costimulatory domains, with potential antineoplastic and immunostimulating activities. Upon re-introduction into the patient, the autologous anti-MUC1*-CAR-4-1BB-CD3zeta-expressing T-lymphocytes specifically recognize and induce selective toxicity in MUC1*-expressing tumor cells. MUC1* is a post-translationally modified form of MUC1, a single pass type I transmembrane protein that is normally expressed in the glandular or luminal epithelial cells of the esophagus, stomach, duodenum, pancreas, uterus, prostate, and lungs, and may be aberrantly expressed in certain tumor types. MUC1* is a growth factor that is activated by ligand-induced dimerization of its extracellular domain, which may stimulate mitogen-activated protein kinase (MAP kinase, MAPK) signaling and promote tumor cell growth. MUC1* is frequently expressed in certain cancer types, with increased expression noted in higher grade lesions and tumor cells resistant to certain chemotherapies.

• Autologous anti-muc1/cd33/cd38/cd56/cd123 gene-engineered car-t cells - A preparation of genetically modified autologous T-cells transduced with lentiviral vectors expressing chimeric antigen receptors (CARs) specific for the tumor-associated antigens (TAAs) mucin 1 (Muc1; MUC1), cluster of differentiation 33 (CD33), CD38, CD56 and CD123 (interleukin-3 receptor alpha chain or IL3RA), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous anti-Muc1/CD33/CD38/CD56/CD123 gene-engineered CAR-T cells are directed to and induce selective toxicity in Muc1/CD33/CD38/CD56/CD123-expressing tumor cells. Muc1/CD33/CD38/CD56/CD123 are present on certain tumor cell types and are minimally expressed on normal, healthy cells. Expression of these TAAs are correlated with poor prognosis. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules included in the CARs, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.

• Autologous anti-ny-eso-1 mtcr retroviral vector transduced pbls - Human autologous peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding both alpha and beta chains of a murine T-cell receptor (mTCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous anti-NY-ESO-1 mTCR retroviral vector transduced PBLs bind to NY-ESO-1 expressed on tumor cells. This may result in cytotoxic T-lymphocyte (CTL)-mediated killing of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types.

• Autologous anti-pd-1 antibody-activated tumor-infiltrating lymphocytes - A preparation of autologous tumor infiltrating lymphocytes (TILs) activated by an anti-programmed cell death protein 1 (PD1) antibody, with potential immunomodulating activity. The autologous TILs are isolated from an autologous tumor sample and ex-vivo activated in the presence of anti-PD-1 antibody. Upon infusion of the autologous anti-PD1 antibody-activated TILs back into the patient, the cells specifically target and kill the patient's tumor cells.

• Autologous anti-psca-car-4-1bb/tcrzeta-cd19t-expressing t-lymphocytes - A preparation of autologous T-lymphocytes that have been immunomagnetically depleted of CD14+ myeloid cells and CD25+ regulatory T-cells (Tregs), activated with anti-CD3 and anti-CD28 beads, and transduced with a self-inactivating (SIN) lentiviral vector (LV) encoding a chimeric antigen receptor (CAR) containing a prostate stem cell antigen (PSCA)-specific, humanized and affinity matured A11 single chain variable fragment (scFv), a human immunoglobulin G4 (IgG4) Fc spacer lacking the CH2 domain, a human CD4 transmembrane domain, a costimulatory human 4-1BB (CD137) cytoplasmic signaling domain linked to the zeta chain of the human T-cell receptor (TCR)/CD3 complex (CD3zeta), and a truncated human CD19 sequence (CD19t), with potential immunostimulating and antineoplastic activities. Upon intravenous infusion, the autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes recognize and induce selective toxicity in PSCA-expressing tumor cells. PSCA, a glycosyl-phosphatidylinositol (GPI)-linked cell surface antigen, is uniquely and highly expressed in certain cancers including bladder, pancreatic, and prostate cancers. Co-expression of CD19t provides an inert, non-immunogenic surface marker that allows for measurement of genetically modified cells and tracking of T-cells following adoptive transfer. The costimulatory signaling domains improve T-cell function, selectivity, expansion and survival.

• Autologous anti-psma car-t cells p-psma-101 - A preparation of autologous T-cells that are enriched to be primarily stem memory T-cells (Tscm) and are transfected by electroporation with a proprietary transposon-based DNA plasmid vector (PiggyBac), encoding both a chimeric antigen receptor (CAR) based on a proprietary non-immunoglobulin scaffold molecule Centyrin (CARTyrin), which specifically recognizes the tumor-associated antigen (TAA) prostate-specific membrane antigen (PSMA), and a human-derived safety switch that can be activated by rimiducid, with potential immunostimulating and antineoplastic activities. Upon administration, autologous anti-PSMA CAR-T cells P-PSMA-101 specifically recognize and induce selective toxicity in PSMA-expressing tumor cells. Use of CARTyrin may elicit less immunotoxicity than CAR T-cells based on antibody-derived single chain variable fragments (scFv), and may allow for increased persistence and decreased exhaustion for the administered T-cells. If significant side effects occur, the safety switch mechanism can be activated by the administration of rimiducid, which results in the rapid attenuation or elimination of P-PSMA-101. PSMA is overexpressed on the surface of metastatic and hormone-refractory prostate cancer cells.

• Autologous anti-psma gene-modified t-lymphocytes - Autologous prostate specific membrane antigen (PSMA) gene-modified T lymphocytes with potential antineoplastic activity. Human autologous T-lymphocytes are isolated and transduced ex vivo with a retrovirus encoding a chimeric immune receptor (CIR) consisting of an antibody fragment against PSMA fused with signaling domains of the T cell. Upon reintroduction into the patient, autologous anti-PSMA gene-modified T-cells bind to PSMA-expressing prostate cancer cells, which may result in specific cytotoxic T-lymphocyte (CTL) tumor cell killing.

• Autologous anti-slamf7 car-expressing t-cells - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) recognizing human SLAM family member 7 (SLAMF7; CD319 CRACC; CS-1) with potential antineoplastic activity. Upon intravenous administration, the autologous anti-SLAMF7 CAR-expressing T-cells target and induce selective toxicity in SLAMF7-expressing tumor cells. SLAMF7 is a member of the signaling lymphocytic activation molecule (SLAM) family of transmembrane receptors that modulate the function of immune cells through immunoreceptor tyrosine-based switch motifs (ITSMs) and intracellular adaptor proteins. SLAMF7 is highly expressed on certain malignant plasma cells and is minimally expressed on healthy immune cells.

• Autologous axl-targeted car t-cells cct301-38 - A preparation of genetically modified autologous T-lymphocytes transduced with a lentiviral vector to express a chimeric antigen receptor (CAR) targeting the receptor tyrosine kinase (RTK) AXL, with potential immunomodulatory and antineoplastic activities. After isolation, transduction, and expansion in culture, the CCT301-38 cells are reintroduced into the patient and are activated within the tumor microenvironment (TME) using proprietary Conditionally Active Biologic (CAB) technology. Upon activation, CAB antibodies bind to a proprietary T-cell signaling domain, promoting T-cell recognition and killing of AXL-expressing tumor cells. AXL is a RTK and oncogene that is overexpressed in many cancer types and is involved in the stimulation of tumor cell proliferation.

• Autologous b-cell/monocyte-presenting her2/neu antigen vaccine bvac-b - An autologous vaccine composed of the antigen presenting cells (APCs) B-lymphocytes and monocytes presenting the tumor-associated antigen (TAA) human epidermal growth factor receptor type 2 (HER2/neu; HER-2; EGFR2; ErbB2). Upon administration of the autologous B-cell- and monocyte-presenting HER2/neu antigen vaccine BVAC-B, the APCs may stimulate the immune system to mount a HER2/neu-specific cytotoxic T-lymphocyte (CTL) immune response as well as a natural killer (NK) cell, and antibody-mediated immune response against HER-2/neu-positive tumor cells, which may result in tumor cell death and decreased tumor growth. HER-2, a tyrosine kinase receptor for epidermal growth factor (EGF), is overexpressed by a variety of tumors.

• Autologous bcma-4-1bbz-targeted car t-cells - A preparation of autologous T-lymphocytes that have been ex vivo transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) containing a single chain variable fragment (scFv) specific for the human tumor-associated antigen (TAA) B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) fused to the co-stimulatory domain of 4-1BB (CD137), and the CD3-zeta (CD3z) T-cell signaling domain (4-1BBz), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous BCMA-4-1BBz-targeted CAR T-cells specifically recognize and induce selective toxicity in BCMA-expressing tumor cells. BCMA, a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF). BCMA is found on the surfaces of plasma cells; it is overexpressed on malignant plasma cells, and plays a key role in plasma cell survival.

• Autologous bcma-targeted car t cells cc-98633 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential immunostimulating and antineoplastic activities. Upon administration, autologous BCMA-targeted CAR T cells CC-98633 specifically recognize and kill BCMA-expressing tumor cells. BCMA, a tumor specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a key role in plasma cell survival; it is found on the surfaces of plasma cells and overexpressed on malignant plasma cells.

• Autologous bcma-targeted car t cells lcar-b4822m - A preparation of autologous peripheral blood T-lymphocytes (PBTLs) that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17), with potential immunostimulating and antineoplastic activities. Upon administration, autologous BCMA-targeted CAR T-cells LCAR-B4822M specifically recognize and kill BCMA-expressing tumor cells. BCMA, a tumor specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a key role in plasma cell survival; it is found on the surfaces of plasma cells and overexpressed on malignant plasma cells.

• Autologous bispecific bcma/cd19-targeted car-t cells gc012f - A preparation of autologous T-lymphocytes engineered to express two separate chimeric antigen receptors (CARs) targeting the tumor-associated antigens (TAAs) BCMA and CD19 and fused to as of yet not fully elucidated co-stimulatory domains, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous bispecific BCMA/CD19-targeted CAR-T cells GC012F specifically and simultaneously target and bind to tumor cells expressing BCMA and/or CD19. This induces selective toxicity in tumor cells that express BCMA and/or CD19. BCMA, a tumor-specific antigen and a receptor for both a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF), is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and plays a key role in the survival of B-lymphocytes and plasma cells. BCMA is found on the surfaces of B-cells and is overexpressed on malignant plasma cells. CD19 is a B-cell-specific cell surface antigen overexpressed in B-cell lineage malignancies. The processing platform used, FasT CAR-T, shortens the manufacturing time to produce the CAR-T cells within 24 hours.

• Autologous bispecific cd19/cd22-targeted car-t cells gc022 - A preparation of autologous human T-lymphocytes engineered to express chimeric T-cell receptors (chimeric antigen receptors or CARs) targeting the tumor-associated antigens (TAAs) CD19 and CD22 and fused to as of yet not fully elucidated co-stimulatory domains, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous bispecific CD19/CD22-targeted CAR-T cells GC022 bind to CD19 and CD22 on the surface of, and induce selective toxicity against, tumor cells expressing CD19 and CD22. CD19 and CD22, both transmembrane phosphoglycoproteins expressed on the surface of cells in the B lineage, are overexpressed on malignant B-cells.

• Autologous bladder cell carcinoma rnas/cd40l rna electroporated autologous matured dendritic cells - A cell-based preparation in which autologous, mature dendritic cells (DCs) are electroporated with in vitro transcribed (IVT) RNAs encoding for a synthetic form of T-cell protein CD40 ligand (CD40L) and IVT RNA encoding for autologous tumor-associated antigens (TAAs) derived from patient-specific bladder cell carcinoma (BCC) cells, with potential immunostimulatory and antineoplastic activities. Upon electroporation into autologous DCs, the RNA is translated and processed. BCC-specific antigenic peptides are subsequently presented via major histocompatibility complex (MHC) Class I molecules on the DCs surface. When AGS-003-BLD is reintroduced to the patient, the MHC-presented peptides interact with and activate CD8-positive T-cells, which elicits a highly specific cytotoxic T-cell (CTL) response against tumor cells expressing the patient-specific BCC TAAs. The signal cascade initiated by expression of the co-stimulatory molecule CD40L results in the secretion of the inflammatory cytokine IL-12, which further stimulates CTLs.

• Autologous blinatumomab-expanded t-cells - A preparation of autologous, peripheral blood-derived polyclonal activated T-cells that have been expanded and activated ex-vivo using blinatumomab and recombinant human IL2 (rhIL-2) and depleted of contaminating CD19+ tumor cells, with potential immunomodulating activity. Upon administration, these blinatumomab-expanded T-cells (BET), composed of functional polyclonal CD4+ and CD8+ T-cells and mostly effector and central memory cells, may induce immunological recovery. BET cell expansion leads to the lysis and elimination of contaminating CD19+ tumor cells. The elimination of contaminating tumor cells is important in the treatment of non-Hodgkin CD20 + indolent lymphoma (iNHL) and chronic lymphatic leukemia (CLL).

• Autologous bone marrow-derived cd34/cxcr4-positive stem cells amr-001 - A cell-based product containing autologous bone marrow derived CD34 positive and C-X-C chemokine receptor type 4 (CXCR4) positive stem cells with potential antiapoptotic and proangiogenic activities. Upon intracoronary infusion after a myocardial infarction (MI), autologous bone marrow-derived CD34/CXCR4-positive stem cells may preserve cardiac muscle cells and prevent apoptosis; thus improving myocardial perfusion. CD34/CXCR4-positive stem cells are naturally mobilized upon cell injury through signaling by hypoxia inducing factor (HIF), which is secreted in response to hypoxia. In turn, HIF induces the synthesis of stromal-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) which mobilize CD34/CXCR4 positive stem cells; CXCR4 is the receptor for stromal-derived factor 1 (SDF-1).

• Autologous car-mbil15-safety switch t-cells prgn-3005 - A preparation of autologous T-lymphocytes that have been genetically modified to co-express three transgenes using the Sleeping Beauty (SB) transposon system and include a chimeric antigen receptor (CAR) targeting an undisclosed tumor-associated antigen (TAA), a membrane-bound IL-15 (mbIL15) and a safety/kill switch, with potential immunostimulating and antineoplastic activities. Upon introduction of the autologous PRGN-3005 into the patient, the T-cells target and bind to the TAA-expressing tumor cells, thereby inducing selective toxicity in the TAA-expressing tumor cells. IL-15 is a pro-survival cytokine that is required for the maintenance of long-lived CD8+ memory T-cells and use of mbIL15 preserves T stem-cell memory (TSCM) through sustained IL-15 signaling, improves T-cell persistence and potentiates the immune response against tumor cells. The safety switch can promote selective elimination of the CAR-T cells. The SB system permits integration of the CAR, the IL-15 fusion variant and safety switch transgenes into T-cells without the need for viral vectors and accelerates the manufacturing process.

• Autologous car-mbil15-safety switch t-cells prgn-3006 - A preparation of autologous T-lymphocytes that have been genetically modified to co-express three transgenes using the Sleeping Beauty (SB) transposon system, including a chimeric antigen receptor (CAR) targeting an undisclosed tumor-associated antigen (TAA), a membrane-bound IL-15 (mbIL15) and a safety/kill switch, with potential immunostimulating and antineoplastic activities. Upon introduction of the autologous PRGN-3006 T-cells into the patient, these T-cells target, bind to and induce selective toxicity in cells expressing this particular TAA. IL-15 is a pro-survival cytokine that is required for the maintenance of long-lived CD8+ memory T-cells. Use of mbIL15 preserves T stem-cell memory (TSCM) through sustained IL-15 signaling, improves T-cell persistence and potentiates the immune response against tumor cells. The safety switch can promote selective elimination of the CAR-T cells. The SB system permits integration of the CAR, the IL-15 fusion variant and safety switch transgenes into T-cells without the need for viral vectors and accelerates the manufacturing process.

• Autologous ccr4-cd30car-cd28-cd3zeta-expressing t-lymphocytes - A preparation of autologous T-lymphocytes (ATL) that have been transduced with the retroviral vector SFG, a Moloney murine leukemia (Mo-MuLV) virus-based vector, encoding human C-C chemokine receptor 4 (CCR4), linked via an internal ribosome entry site (IRES), to a chimeric antigen receptor (CAR) composed of a single chain single-chain variable fragment (scFv) directed against the CD30 antigen (CAR.CD30) and linked, via the spacer human IgG1 immunoglobulin heavy constant region (hinge-CH2CH3 region), to the co-stimulatory domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta), with potential immunostimulating and antineoplastic activities. Upon administration of the autologous CCR4-CD30CAR-CD28-CD3zeta-expressing T-lymphocytes, the expressed CCR4 on the T-cells allows for enhanced migration of the cells to chemokine-secreting tumor cells. The expressed CAR.CD30 moiety specifically recognizes and binds to CD30-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD30, a cell surface receptor and a member of the tumor necrosis factor (TNF) receptor superfamily, is transiently expressed on activated lymphocytes and is constitutively expressed in hematologic malignancies. CCR4, a G-coupled-protein receptor for C-C chemokines normally expressed on regulatory T-cells (Tregs) but not on cytotoxic T-lymphocytes (CTLs), is involved in chemokine-mediated cellular migration. The co-expression of CCR4 on these CTLs may enhance their anti-tumor activity compared to T-lymphocytes expressing the same CAR-CD30 receptor but without CCR4 expression.

• Autologous cd123-4scar-expressing t-cells 4scar123 - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-CD123 (interleukin-3 receptor alpha chain or IL3RA) single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon administration, autologous CD123-4SCAR-expressing T-cells 4SCAR123 are directed to and induce selective toxicity in CD123-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.

• Autologous cd123car-cd28-cd3zeta-egfrt-expressing t lymphocytes - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a hinge-optimized, chimeric antigen receptor (CAR), containing a CD28 co-stimulatory signaling domain fused to CD3 zeta, the single-chain variable fragment of CD123 (Interleukin-3 receptor alpha chain or IL3RA) antigen, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD123CAR-CD28-CD3zeta-EGFRt-expressing T Lymphocytes are directed to and induce selective toxicity in CD123-expressing tumor cells. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates detection of the administered T-cells in vivo and can promote elimination of those cells following a cetuximab-induced antibody-dependent cellular cytotoxicity response. The costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity. Hinge optimization prevents recognition of the CAR by Fc receptors (FcRs).

• Autologous cd123car-cd28-cd3zeta-egfrt-expressing t lymphocytes mb-102 - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating (SIN) lentiviral vector expressing a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD123 (interleukin-3 receptor alpha chain or IL3RA) and linked to the CD28 co-stimulatory signaling domain fused to CD3 zeta, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD123CAR-CD28-CD3zeta-EGFRt-expressing T lymphocytes MB-102 are directed to and induce selective toxicity in CD123-expressing tumor cells. CD123, a subunit of the heterodimeric interleukin-3-receptor (IL-3R), is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates detection of the administered T-cells in vivo and can promote elimination of those cells following a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response.

• Autologous cd133-positive btsc mrna-pulsed autologous dendritic cell vaccine - A cancer vaccine consisting of autologous dendritic cells (DCs) loaded with CD133-positive autologous brain tumor stem cells (BTSCs) -derived mRNA with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, autologous CD133-positive BTSC mRNA-pulsed autologous dendritic cell vaccine may elicit a cytotoxic T-lymphocyte (CTL) response against the CD133-positive BTSCs from which the autologous tumor mRNA is derived. CD133, a tumor-associated antigen (TAA) and neural stem cell marker, has been found on a specific subset of glioblastoma multiforme (GBM) stem cells; its presence has been correlated with resistance to conventional chemotherapy and radiotherapy.

• Autologous cd138-specific car t-cells - A preparation of autologous T-lymphocytes that have been engineered to express a chimeric antigen receptor (CAR) specific for syndecan-1 (CD138), with potential immunomodulating and antineoplastic activities. Upon administration, the autologous CD138 CAR-expressing T-cells target and induce selective toxicity in syndecan-1-expressing tumor cells. Syndecan-1, a type 1 transmembrane proteoglycan and tumor-associated antigen (TAA), is overexpressed in a variety of cancer cells and plays a key role in the regulation of cell growth, differentiation, and adhesion.

• Autologous cd171-specific car-cd28 zeta-4-1-bb-egfrt-expressing t lymphocytes - A preparation of genetically modified autologous human T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) specific for the L1 cell adhesion molecule (L1-CAM/CD171) antigen, and the co-stimulatory signaling domains CD28, 4-1BB (CD137) and CD3 zeta, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon re-infusion into the patient, the autologous L1-CAM-specific CAR-CD28 zeta-4-1-BB-EGFRt-expressing T-lymphocytes are directed to and induce selective toxicity in L1-CAM-expressing tumor cells. L1-CAM, a neuronal cell adhesion molecule and member of the L1 protein family, plays a key role in the development of the nervous system; it is overexpressed in various tumor cell types and is associated with increased chemoresistance, tumor progression, migration and metastasis. Devoid of both ligand-binding domains and tyrosine kinase activity, EGFRt facilitates both the detection of the administered T-cells in vivo and the elimination of the modified T-cells following a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. The co-stimulatory signaling domains enhance both proliferation of T-cells and antitumor activity.

• Autologous cd19 car+ egfrt + cd4+ and cd8+ t cells - A preparation of a defined ratio of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv), derived from the CD19-specific murine immunoglobulin (Ig) G1 monoclonal antibody FMC63, fused to the signaling domain of CD28, the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD19 CAR+ EGFRt + CD4+ and CD8+ T-cells are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.

• Autologous cd19 car-expressing cd4+/cd8+ t-cells mb-cart19.1 - A preparation of CD4+ and CD8+ autologous T-lymphocytes transduced with the lentiviral vector pLTG1563 expressing a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD19 CAR-expressing CD4+/CD8+ T-cells MB-CART19.1 are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous cd19 car-expressing t-cells ytb323 - A preparation of autologous T-lymphocytes that are genetically engineered to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD19 CAR-expressing T-cells YTB323 are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous cd19/cd22 chimeric antigen receptor t-cells - A preparation of autologous human T-lymphocytes engineered to express a chimeric T-cell receptor (chimeric antigen receptor or CAR) consisting of one or more binding domains targeting the tumor-associated antigens (TAAs) CD19 and CD22 and fused to one or more co-stimulatory TCR-signaling domains, with potential immunostimulating and antineoplastic activities. Upon administration, the autologous CD19/CD22 CAR T-cells bind to CD19 and CD22 on the surface of, and induce selective toxicity against, tumor cells expressing CD19 and CD22. CD19 and CD22, both transmembrane phosphoglycoproteins expressed on the surface of cells in the B lineage, are overexpressed on malignant B-cells.

• Autologous cd19/pd-1 bispecific car-t cells - A preparation of autologous T-lymphocytes that are transduced with a lentiviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19) and a programmed cell death protein 1 (PD1)/CD28 chimera, with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, the autologous CD19/PD-1 bispecific CAR-T cells target and bind to CD19 and the PD-1 ligands, programmed cell death ligand 1 (PD-L1) and 2 (PD-L2), expressed on tumor cells. The binding to CD19 leads to a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and cell lysis of these cells. The binding of the PD1/CD28 chimera to PD-L1 prevents the normal PD1/PD-L1-mediated T-cell suppression and, instead, promotes signaling through the CD28 domain, which results in the stimulation of T-lymphocytes. This enhances T-lymphocyte proliferation and anti-tumor activity. CD19 antigen is a B-cell specific cell surface antigen overexpressed in B-cell lineage malignancies. PD-1 protein, found on activated T-cells, negatively regulates T-cell activity. It plays a key role in immune evasion and prevents tumor cell lysis. The construct of the PD1/CD28 chimera converts PD-L1 into a co-stimulation ligand of primary human CD8+ cytotoxic T-lymphocytes (CTLs). CD28 is a costimulatory molecule expressed by T-cells that enhances T-lymphocyte proliferation and activity.

• Autologous cd19-28z chimeric antigen receptor-expressing t-lymphocytes - Genetically modified autologous T-lymphocytes transduced with a replication incompetent retroviral vector expressing a chimeric T cell antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment), fused to the extracellular, transmembrane and intracellular signaling domains of the T cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (CAR19-28z), with potential antineoplastic activities. Upon intravenous administration, autologous CD19-28z CAR-expressing T-lymphocytes are directed to CD19-expressing tumor cells, which induces selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The CD28 co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. The inclusion of the CD28 signaling domain may increase proliferation of T-cells and antitumor activity compared to the inclusion of the CD3-zeta chain alone.

• Autologous cd19car-cd28-cd137/cd27/cd3zeta-icasp9-expressing t-lymphocytes - Autologous T-lymphocytes that have been transduced with a fourth generation-lentiviral vector to express the 4SCAR19 gene composed of a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) of anti-CD19 coupled to the co-stimulatory molecules CD28, 4-1BB (CD137), and CD27, and to the cytoplasmic portion of the zeta chain of the human T-cell receptor (CD3zeta), and containing the apoptosis-inducible suicide gene human caspase 9 (iCASP9 or iC9), that is linked to a drug binding domain, with potential immunostimulating and antineoplastic activities. The iCASP9 construct consists of the entire coding sequence for the human FK506-drug binding protein (FKBP12) with an F36V mutation (FKBP12-F36V) that is linked to the gene encoding iC9, which is a modified form of the CASP9 gene where the sequences encoding the endogenous caspase activation and recruitment domains have been deleted. Upon transfusion, anti-CD19-CAR-CD28/CD137/CD27/CD3zeta-iCasp9-expressing autologous T-lymphocytes target and bind to CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells, and causes tumor cell lysis. If the administered T-cells cause unacceptable side effects, the chemical homodimerizer AP1903, which binds to the FKBP12-F36V drug-binding domain, can be administered; this induces caspase 9 expression, and results in apoptosis of the administered 4SCAR19 T-cells. CD19, cluster of differentiation 19, is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. Incorporation of the costimulatory signaling domains increases human T-cell function, expansion, and survival.

• Autologous cd19car-cd28-cd3zeta-egfrt-expressing tcm-enriched t cells - A preparation of genetically modified autologous central memory (Tcm) enriched T-cells transduced with a replication incompetent lentiviral vector expressing a chimeric antigen receptor (CAR), containing a CD28 signaling domain fused to both CD3 zeta, which targets the CD19 antigen, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells are directed to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered T-cells and can promote elimination of those cells upon a cetuximab-induced antibody dependent cellular cytotoxicity response. The costimulatory signaling domain enhances proliferation of T cells and antitumor activity.

• Autologous cd19car-cd28-cd3zeta-egfrt-expressing tn/mem-enriched t-lymphocytes - A preparation of genetically modified autologous lymphocytes comprised of CD62L-positive naïve and memory T-cells (Tn/mem), that are transduced ex vivo with a self-inactivating (SIN) lentiviral vector expressing a hinge-optimized chimeric antigen receptor (CAR) specific for the CD19 antigen and containing CD28 and CD3 zeta signaling domains, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon isolation of peripheral blood lymphocytes (PBLs), transduction of the CD62L-positive T-lymphocytes, expansion ex vivo and reintroduction of the cells into the patient, the autologous CD19R(EQ)-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-cells target CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered T-cells and can promote elimination of those cells upon a cetuximab-induced antibody dependent cellular cytotoxicity response. Tn/mem T-cells include naïve T-cells, central memory T-cells (Tcm) and stem cell memory T-cells (Tscm). CD19R(EQ) contains two point mutations in the immunoglobulin (Ig) G4 spacer region, thereby preventing recognition of the CAR by Fc receptors (FcRs).

• Autologous cd19-cd8-cd28-cd3zeta-car-mbil15-her1t t cells - A preparation of autologous, genetically modified T-lymphocytes, that have been electroporated ex vivo with sleeping beauty (SB)-derived DNA plasmids, expressing a second-generation chimeric antigen receptor (CAR) composed of a mouse single-chain variable fragment (scFv) specific for the tumor-associated antigen (TAA) cluster of differentiation 19 (CD19) that is linked to the co-stimulatory molecules T-cell surface glycoproteins CD8 and CD28 and the zeta chain of the T-cell receptor (TCR)/CD3 complex (CD3-zeta) and co-expressed with a chimeric membrane-bound fusion protein comprised of interleukin-15 (IL-15) fused to IL-15 receptor (mbIL15) and a safety/kill switch composed of a truncated form of the human epidermal growth factor receptor (ErbB1t; EGFR) (HER1t), with potential immunostimulating and antineoplastic activities. Upon reintroduction of the autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells into the patient, the T-cells target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. HER1t can promote selective elimination of the CAR-T cells through cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). IL-15 is a pro-survival cytokine that is required for the maintenance of long-lived CD8+ memory T-cells and use of mbIL15 preserves T stem-cell memory (TSCM) through sustained IL-15 signaling, improves T-cell persistence and potentiates the immune response against tumor cells. The SB system permits electroporation of the CAR, the IL-15 fusion variant and safety switch transgenes into T-cells without the need for viral vectors and accelerates the manufacturing process.

• Autologous cd19-targeted car t cells cc-97540 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) CD19, with potential immunostimulating and antineoplastic activities. Upon administration, autologous CD19-targeted CAR T cells CC-97540 specifically target and bind to CD19-expressing tumor cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells and tumor cell lysis. CD19, cluster of differentiation 19, is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors.

• Autologous cd19-targeted car t cells jwcar029 - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19 and containing, as of yet undisclosed, costimulatory signaling domains, with potential immunostimulating and antineoplastic activities. Upon administration, autologous CD19-targeted CAR T-cells JWCAR029 target and bind to CD19-expressing tumor cells, thereby inducing selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.

• Autologous cd19-targeted car-t cells gc007f - A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) consisting of a single chain variable fragment (scFv) of anti-CD19 coupled to as of yet not fully elucidated co-stimulatory molecules, with potential immunostimulating and antineoplastic activities. Upon transfusion, autologous CD19-targeted CAR-T cells GC007F target and bind to CD19-expressing neoplastic B-cells. This results in a cytotoxic T-lymphocyte (CTL) response against CD19-expressing tumor cells, the release of cytotoxic molecules and the induction of tumor cell lysis. CD19, cluster of differentiation 19, is a B-cell-specific cell surface antigen overexpressed in B-cell lineage tumors. The processing platform used, FasT (F) CAR-T, shortens the manufacturing time to produce the CAR-T cells within 24 hours.

• Autologous cd20-4scar-expressing t-cells 4scar20 - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-CD20 single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD20-4SCAR-expressing T-cells 4SCAR20 are directed to and induce selective toxicity in CD20-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. CD20 is a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell malignancies. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.

• Autologous cd22-4scar-expressing t-cells 4scar22 - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-CD22 single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD22-4SCAR-expressing T-cells 4SCAR22 are directed to and induce selective toxicity in CD22-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. CD22, a B-lineage-restricted, transmembrane phosphoglycoprotein, is expressed on malignant B cells. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.

• Autologous cd30car-cd28-cd3zeta-expressing t-lymphocytes - A preparation of autologous T-lymphocytes (ATL) that have been transduced with the retroviral vector SFG, a Moloney murine leukemia (Mo-MuLV) virus-based vector, encoding a chimeric antigen receptor (CAR) composed of a single chain single-chain variable fragment (scFv) directed against the CD30 antigen (CAR.CD30) and linked, via the spacer human IgG1 immunoglobulin heavy constant region (hinge-CH2CH3 region), to the co-stimulatory domains of CD28 and the zeta chain of the TCR/CD3 complex (CD3-zeta) (CD28zeta), with potential immunostimulating and antineoplastic activities. Upon administration, the autologous CD30CAR-CD28-CD3zeta-expressing T-lymphocytes specifically recognize and bind to CD30-expressing tumor cells, resulting in specific T-cell-mediated tumor cell lysis. CD30, a cell surface receptor and a member of the tumor necrosis factor (TNF) receptor superfamily, is transiently expressed on activated lymphocytes and is constitutively expressed in hematologic malignancies.

• Autologous cd34+-enriched hspcs transduced with vsv-g encoding ifn-a2 - A preparation of autologous CD34+-enriched hematopoietic stem and progenitor cells (HSPCs) that are genetically modified with a vesicular stomatitis virus-G (VSV-G) pseudo-typed lentiviral vector encoding for the human cytokine interferon-alpha 2 (IFN-a2) gene, with potential immunostimulating and antineoplastic activities. The expression of IFN-a2 is tightly controlled by the human angiopoietin receptor Tie2 enhancer/promoter sequence, found in the tumor-infiltrating macrophages Tie2 expressing monocytes (TEMs), and is under microRNA-126 (miR-126)-mediated control. This enables suppression of IFN-a2 expression in HSPCs while IFN-a2 is selectively expressed in TEMs. Upon administration of the autologous CD34+-enriched HSPCs transduced with VSV-G encoding IFN-a2, the HSPCs travel to the bone marrow and differentiate into various cells including monocytes and macrophages. These cells travel to the tumor microenvironment (TME), and the TEMs, capable of expressing IFN-a2, specifically release IFN-a2 in the TME. IFN-2a binds to specific IFN cell-surface receptors, and activates IFN-mediated signal transduction, resulting in the transcription and translation of genes containing an interferon-specific response element whose protein products mediate anticancer and anti-angiogenic effects. This results in the induction of both G2 cell cycle arrest and apoptosis in tumor cells. In addition, IFN-a2 triggers an indirect anti-tumor immune response involving the activation of natural killer (NK) cells and dendritic cells (DCs), and the induction of immune effector cell cytotoxicity, thereby further killing tumor cells. TEMs, a subset of tumor-infiltrating macrophages characterized by expression of the tyrosine protein kinase angiopoietin receptor Tie2, are upregulated in the TME while infrequently found in normal organs. TEMs promote tumor angiogenesis.

• Autologous cd38-4scar-expressing t-cells 4scar38 - A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a fourth generation chimeric antigen receptor (4SCAR) consisting of an anti-CD38 single chain variable fragment (scFv) that is coupled to the costimulatory signaling domains CD28, CD137, CD27 and the zeta chain of the T-cell receptor (TCR), and is fused with the suicide gene inducible caspase 9 (iCasp9), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD38-4SCAR-expressing T-cells 4SCAR38 are directed to and induce selective toxicity in CD38-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered. AP1903 binds to the drug binding FKBP12-F36V domain and induces activation of caspase 9, which results in the apoptosis of the administered T-cells and enhances safety of this agent. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies, and its expression has been correlated with poor prognosis. CD28, CD137 and CD27, T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation and enhance both proliferation of T-cells and antitumor activity.

• Autologous cd4+/cd8+ 4-1bb-cd3zeta-egfr806-car-egfrt/4-1bb-cd3zeta-cd19-car-her2tg-expressing cars t cells - A preparation of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector that co-expresses two different second generation chimeric antigen receptors (CARs), one composed of a short chain variable fragment (scFv) binding domain derived from depatuxizumab, a human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb806; ABT-806), coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta) and the signaling domain of 4-1BB (CD137), and linked to a truncated form of the human epidermal growth factor receptor (EGFRt), and one composed of a short chain variable fragment (scFv) binding domain derived from an anti-CD19 monoclonal antibody, coupled to CD3-zeta) and 4-1BB, and linked to a truncated form of the human epidermal growth factor receptor 2 (HER2tG), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD4+/CD8+ 4-1BB-CD3zeta-EGFR806-CAR-EGFRt/4-1BB-CD3zeta- CD19-CAR-HER2tG-expressing CARs T-cells are directed to, bind to, and induce selective toxicity in EGFR deletion mutation variant III (EGFRvIII)-expressing tumor cells. The binding of these T-cells to CD19 expressed on B-cells enhances their expansion and prolongs their persistence in vivo, thereby increasing the efficacy of these CAR T-cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt and HER2tG facilitate in vivo detection of the administered, transduced T-cells and can promote elimination of these cells through an antibody-dependent cellular cytotoxicity (ADCC) response. HER2tG allows for enhanced binding by trastuzumab. EGFRvIII, an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types but absent in normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy. Depatuxizumab specifically targets abnormal conformational states of EGFR, including EGFRvIII, and activating mutations, with lower affinity for wild-type EGFR. CD19, a transmembrane phosphoglycoprotein is expressed on the surface of cells in the B-lineage.

• Autologous cd4+/cd8+ egfr806 specific 4-1bb-cd3zeta-egfrt-expressing car t cells - A preparation of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) composed of a short chain variable fragment (scFv) binding domain derived from depatuxizumab, a human anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb806; ABT-806), coupled to the zeta chain of the TCR/CD3 complex (CD3-zeta) and the signaling domain of 4-1BB (CD137), and linked to a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Depatuxizumab specifically targets abnormal conformational states of EGFR, including the EGFR deletion mutation variant III (EGFRvIII), and activating mutations, with very low affinity for wild-type EGFR. Upon intravenous administration, the autologous CD4+/CD8+ EGFR806 specific 4-1BB-CD3zeta-EGFRt-expressing CAR T-cells are directed to and induce selective toxicity in EGFRvIII-expressing tumor cells. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of these cells through an anti-EGFR antibody-dependent cellular cytotoxicity (ADCC) response. EGFRvIII, an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types but absent in normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy.

• Autologous cd40l-expressing b-cll vaccine - A cancer vaccine consisting of autologous, B-chronic lymphocytic leukemia (B-CLL) cells harvested from a patient and transduced with an adenoviral vector encoding the gene for the human CD40 ligand (CD40L; TRAP; CD154), with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient, the autologous CD40L-expressing B-CLL vaccine expresses the co-stimulatory molecule CD40L, which binds to its cognate receptor, CD40, on antigen presenting cells (APC). This induces apoptosis, stimulates maturation and proliferation of APCs, and facilitates a cytotoxic T-lymphocyte (CTL) response against tumor cells. CD40L is a type II membrane protein that binds to CD40, which is a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor superfamily.

• Autologous cd5-specific car-28 zeta car t-cells - Autologous T-lymphocytes transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD5 single chain variable fragment (scFv) coupled to the costimulatory signaling domain CD28 and the zeta chain of the T-cell receptor (TCR), with potential immunomodulating and antineoplastic activities. Upon transfusion, the autologous CD5-specific CAR-28 zeta CAR T-cells are directed to and induce selective toxicity in CD5-expressing tumor cells. The tumor-associated antigen (TAA) CD5 is a T-cell surface glycoprotein expressed on the surface of normal T-cells, and is overexpressed on various B- and T-cell malignancies; its expression is associated with poor prognosis.

• Autologous cd8 positive pbl sensitized to drosophila cell-presented melanoma peptides - A preparation of autologous CD8+ (cytotoxic) human peripheral blood lymphocytes (PBLs) sensitized to Drosophila cell-presented melanoma peptides, with potential immunostimulating and antineoplastic activities. Autologous CD8+ T-lymphocytes, isolated from a melanoma patient, are exposed in vitro to melanoma peptide-pulsed HLA-A2-expressing Drosophila cells, expanded, and reintroduced into the patient; these tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the melanoma antigens, resulting in tumor cell lysis. Drosophila cells, which do not express any native MHC molecules, have been shown to potently stimulate tumor-reactivity in vitro from human peripheral blood lymphocytes (PBL) when stably transfected with human MHC molecules and appropriate adhesion and costimulatory molecules.

• Autologous cd8+ melanoma specific t cells - Autologous CD8 T-lymphocytes against melanoma-associated antigens, with potential immunomodulating and antineoplastic activities. Following leukapheresis and the ex vivo expansion of cytotoxic T-lymphocytes, the autologous CD8+ melanoma specific T-cells are re-introduced into the melanoma patient. These cytotoxic T-cells recognize and kill the patient's own melanoma cells.

• Autologous cd8+ slc45a2-specific t lymphocytes - A preparation of autologous CD8+ T lymphocytes targeting SLC45A2, a melanoma-associated antigen, with potential immunomodulating and antineoplastic activities. Following peripheral blood mononuclear cell (PBMC) collection and ex vivo expansion of SLC45A2-specific cytotoxic T-lymphocytes (CTLs), the autologous CD8+ SLC45A2-specific CTLs are re-infused into the patient, where they target and lyse SLC45A2-expressing tumor cells. While SLC45A2 is expressed by approximately 80% of cutaneous melanomas, its expression is limited in mature normal melanocytes, allowing high tumor selectivity and reduced potential for autoimmune toxicity.

• Autologous cea-specific cytotoxic t-lymphocytes - Autologous cytotoxic T-lymphocytes (CTLs) specifically reactive to the tumor-associated antigen (TAA) human carcinoembryonic antigen (CEA), with potential antineoplastic activity. Dendritic cells (DCs) isolated from the patient's blood are infected with recombinant adeno-associated virus (AAV) expressing the CEA gene. Exposure of T-lymphocytes to DCs creates CEA-specific CTLs which are expanded. Upon reintroduction of these CTLs into the patient, these cells recognize and kill CEA-expressing tumor cells. CEA, a tumor-associated antigen and a member of the CEA family of proteins, plays a key role in cell migration, cell invasion, and cell adhesion and is overexpressed by a variety of cancer types.

• Autologous cervical cancer-specific engineered immune effector cells - A preparation of autologous immune effector cells genetically modified to target a not yet disclosed cervical cancer-specific tumor-associated antigen (TAA), with potential immunomodulating and antineoplastic activities. After isolation, transduction, expansion in culture, and reintroduction into the patient, the autologous cervical cancer-specific engineered immune effector (CC-EIE) cells bind to and induce selective toxicity in tumor cells expressing the TAA.

• Autologous cish-inactivated tils - A preparation of autologous tumor-infiltrating lymphocytes (TILs) where the cytokine-inducible SH2-containing protein gene (CISH) has been inactivated using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR associated protein 9 (Cas9) editing system, containing guide RNA (gRNA) coupled to a recombinant form of the DNA endonuclease Cas9, with potential immunomodulating and antineoplastic activities. Using the CRISPR/Cas9 system, the autologous TILs are transfected, ex vivo, with a plasmid encoding for a gRNA that site-specifically targets and binds to the human CISH gene. Cas9 cleaves these specific DNA sites, which causes double strand breaks, disrupts the gene encoding CISH and prevents transcription. Upon intravenous administration, the autologous CISH-inactivated TILs are able to induce a T-cell-mediated immune response against tumor cells. CISH, a member of the suppressor of cytokine signaling family (SOCS; cytokine-induced STAT inhibitor; STAT-induced STAT inhibitor; SSI), is induced by T-cell receptor (TCR) stimulation. CISH plays a key role in the negative regulation of both T-cell signaling and CTL-mediated tumor cell eradication. The knockout of the CISH gene enhances the expansion and anti-tumor activities of effector T-cells.

• Autologous cll1-car-cd28-expressing t-lymphocytes - A preparation of autologous T-lymphocytes expressing a chimeric antigen receptor (CAR) specific for the tumor-associated antigen (TAA) C-type-lectin-like molecule-1 (CLL1; C-type lectin domain family 12 member A; CLEC12A) linked to the CD28 co-stimulatory signaling domain, with potential immunomodulating and antineoplastic activities. Upon administration, the autologous CLL1-CAR-CD28-expressing T-lymphocytes specifically target and bind to CLL1-expressing tumor cells. This induces selective toxicity in tumor cells that express the CLL1 antigen. CLL1, a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily, is overexpressed in leukemic stem cells (LSCs) and plays an important role in disease progression and relapse for myeloid malignancies.

• Autologous cll1-cd33 compound car t cells - Autologous T-lymphocytes transduced with a lentiviral vector expressing a compound chimeric antigen receptor (cCAR) containing two CARs, one specific for the CD33 antigen and one specific for the C-type-lectin-like molecule-1 (CLL1; C-type lectin domain family 12 member A; CLEC12A), with potential immunomodulating and antineoplastic activities. Upon administration, the CD33/CLL1-specific CARs lentiviral vector-transduced autologous T-lymphocytes, expressing both the anti-CD33 CAR and the anti-CLL1 CAR on their surfaces, specifically and simultaneously target and bind to CD33- and CLL1-expressing tumor cells, with their anti-CD33 CAR and their anti-CLL1 CAR, respectively. This induces selective toxicity in tumor cells that express the CD33 antigen and the CLL1 antigen. CD33 is expressed on normal non-pluripotent hematopoietic stem cells and is overexpressed on myeloid leukemia cells. CLL1, a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily, is overexpressed in leukemic stem cells (LSCs) and plays an important role in disease progression and relapse for myeloid malignancies.

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