Patritumab

Engineered Monoclonal Antibodies

Diagram of engineered monoclonal antibodies

Engineered monoclonal antibodies are a class of biological therapies that are designed to target specific antigens on the surface of cells. These antibodies are produced using recombinant DNA technologies and are used in the treatment of various diseases, including cancer, autoimmune disorders, and infectious diseases.

Structure and Function

Monoclonal antibodies are composed of two identical heavy chains and two identical light chains, forming a Y-shaped molecule. The tips of the "Y" contain the antigen-binding sites, which are highly specific to the target antigen. This specificity allows monoclonal antibodies to bind to their target with high affinity, blocking or modulating the function of the antigen.

Types of Engineered Monoclonal Antibodies

There are several types of engineered monoclonal antibodies, each designed for specific therapeutic purposes:

• Chimeric antibodies: These antibodies are composed of murine (mouse) variable regions and human constant regions. They are less immunogenic than fully murine antibodies.

• Humanized antibodies: These antibodies are mostly human, with only the antigen-binding sites derived from murine sources. This reduces the risk of immune reactions.

• Fully human antibodies: These are entirely human in origin, produced using transgenic mice or phage display technologies.

• Bispecific antibodies: These antibodies are engineered to bind two different antigens simultaneously, offering unique therapeutic mechanisms.

Applications in Medicine

Engineered monoclonal antibodies have revolutionized the treatment of many diseases:

• Cancer therapy: Monoclonal antibodies can target specific tumor antigens, leading to direct tumor cell killing or recruitment of immune cells to attack the tumor.

• Autoimmune diseases: By targeting specific components of the immune system, monoclonal antibodies can reduce inflammation and tissue damage in diseases such as rheumatoid arthritis and multiple sclerosis.

• Infectious diseases: Monoclonal antibodies can neutralize pathogens or their toxins, providing passive immunity or enhancing the host's immune response.

Production

The production of engineered monoclonal antibodies involves several steps:

1. Antigen identification: The target antigen is identified and characterized. 2. Hybridoma technology: B cells from immunized animals are fused with myeloma cells to create hybridomas that produce the desired antibody. 3. Recombinant DNA technology: Genes encoding the antibody are cloned and expressed in suitable host cells, such as Chinese hamster ovary cells. 4. Purification and formulation: The antibodies are purified and formulated for clinical use.

Challenges and Future Directions

While engineered monoclonal antibodies have shown great promise, there are challenges such as high production costs, potential for immune reactions, and the development of resistance. Ongoing research aims to improve antibody design, reduce immunogenicity, and enhance therapeutic efficacy.

Related Pages

• Monoclonal antibody therapy
• Biopharmaceutical
• Immunotherapy
• Hybridoma technology

Patritumab is an experimental monoclonal antibody designed for the treatment of cancer. It specifically targets and binds to the human epidermal growth factor receptor 3 (HER3), which is involved in the proliferation and survival of certain types of cancer cells. Patritumab is being investigated for its potential use in treating various types of solid tumors, including breast cancer, non-small cell lung cancer (NSCLC), and head and neck cancer.

Development and Mechanism

Patritumab was developed by Daiichi Sankyo, a global pharmaceutical company. The drug operates by targeting HER3, a member of the epidermal growth factor receptor (EGFR) family, which also includes EGFR, HER2, and HER4. These receptors are tyrosine kinases that play critical roles in signaling pathways that regulate cell growth and survival. HER3 is known to be overexpressed in many cancers and is associated with poor prognosis and resistance to existing therapies.

By binding to HER3, patritumab inhibits its interaction with other members of the EGFR family, particularly HER2, thereby blocking the signaling pathways that lead to tumor growth and survival. This mechanism of action makes it a potential therapeutic option in cancers where HER3 plays a significant role.

Clinical Trials

Patritumab has been evaluated in several clinical trials. Early-phase trials have assessed its safety, tolerability, and preliminary efficacy in patients with advanced solid tumors. The results from these trials have provided the basis for further investigation in more targeted patient populations.

One of the notable Phase II trials involved patritumab in combination with erlotinib in patients with NSCLC. However, the study did not meet its primary endpoint of improved progression-free survival compared to erlotinib alone. Despite this, research continues to explore patritumab's potential in different combinations and settings.

Future Directions

Research is ongoing to better understand the role of HER3 in cancer and to optimize the therapeutic strategies involving patritumab. This includes the development of biomarkers to identify patients who are most likely to benefit from HER3-targeted therapies and the investigation of combination therapies that might overcome resistance mechanisms.

See Also

• Monoclonal antibodies for cancer
• Targeted therapy
• Epidermal growth factor receptor

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