Monoclonal antibodies are laboratory-produced molecules that are designed to mimic the immune system’s ability to fight off harmful pathogens, such as viruses or cancer cells.
Monoclonal antibodies are derived from a single type of immune cell, called a B cell.
To create monoclonal antibodies, first an animal, typically a mouse, is immunized with the specific antigen they want to target.
The animal’s immune system then produces a variety of B cells that produce different antibodies against the antigen.
These B cells are then harvested, and the ones producing the desired antibody are fused with immortalized cells in the laboratory to create hybridoma cells.
The hybridoma cells are then cultured and multiplied, producing large amounts of the specific monoclonal antibody.
These antibodies can be purified and used for various applications, such as diagnostics, therapeutics, and research.
Monoclonal antibodies have revolutionized medicine and have been used to treat a wide range of diseases, including cancer, autoimmune disorders, and infectious diseases.
They can target specific molecules on the surface of cells or in the bloodstream, helping to block their function or deliver drugs directly to the affected tissues.
One example of a monoclonal antibody is the drug Herceptin (trastuzumab), which is used to treat certain types of breast cancer that overexpress the HER2 protein.
Herceptin specifically targets and blocks the HER2 protein, preventing cancer cell growth and improving patient outcomes.
Utilizes hybridization of an immortal myeloma cell line to select single cells and clonally expand a single hybrid between the antibody forming cell and the myeloma cell.
Monoclonal antibodies to B-cell surface antigens can induce apoptosis, antibody dependent cellular toxicity and complement related cellular toxicity of lymphoma cells.
Anticancer monoclonal antibodies can mediate anti-tumor effects by cell cycle arrest, direct induction of apoptosis, and sensitization to cytotoxic drugs, complement mediated cytotoxicity, and antibody dependent cellular cytotoxicity.
Immunotherapy drugs can enhance the immunologic response to MET-expressing tumor cells, or actively by stimulating immune cells and altering differentiation/growth of tumor cells.
The administration of monoclonal antibodies (mAbs) is a form of passive Immunotherapy.
Monoclonal antibodies facilitate destruction of tumor cells by complement-dependent cytotoxicity (CDC) and cell-mediated cytotoxicity (ADCC).
In complement-dependent cytotoxicity , the monoclonal antibody binds to specific antigen, leading to activation of the complement cascade, which in turn leads to formation of pores in tumor cells.
In cell-mediated cytotoxicity (ADCC) the Fab domain of a mAb binds to a tumor antigen, and Fc domain binds to Fc receptors present on effector cells, which are phagocytes and NK cells, thus forming a bridge between an effector and a target cells.
Monoclonal antibodies facilitate destruction of tumor cells by complement-dependent cytotoxicity (CDC) and cell-mediated cytotoxicity (ADCC).
Murine monoclonal antibodies may induce human anti-mouse antibodies (HAMA) that attach to the antibody and eliminate it from the circulation.
They bind to the antigens expressed on the tumor cells and bring about their action.
They exert anti-tumor responses by mechanisms to include: direct cytotoxicity by inducing apoptosis or down regulating signals of cell survival, by delivery of cytotoxic and radiotherapeutic agents, by anti-body dependent cell mediated cytotoxicity and complement dependent cytotoxicity and targeting growth factors and vasculature, thereby preventing tumor growth or by targeting the supporting junctions with stromal cells or microenvironment.
Tumor antigen-targeted monoclonal antibody-based immunotherapy using rituximab, trastuzumab, cetuximab, is clinically effective in lymphoma, breast cancer, head and neck cancer and colorectal cancers.
Antigens used as targets are also expressed by a large number of normal cells that can cause allergic reactions and other adverse affects.
Tumor antigen-targeted monoclonal antibodies yield response rates of 8-10% in advanced, heavily pretreated and recurrent disease.
Efficacy is seen in only some of malignant diseases expressing tumor antigen on tumor cells.
A member of the CD28:B7 immunoglobulin family for immune checkpoint monoclonal antibodies, is the CTLA-4.
CTLA-4 functions as an immune checkpoint as it’s binding to the B7 on antigen-presenting cells down regulates T cell activation.
Dozens of antibodies are approved for treatment of wide variety of maladies including: cancers, autoimmune diseases, clotting, abnormalities, and processes of nearly every organ system.
Bioengineering constructs include antibody-drug conjugates that deliver payloads of drugs, toxins, or radionucleotides to a particular cell type.
Parts of antibodies can be grafted onto T cells, which directs their lytic activity to a particular target (chimeric antigen receptor T cells).
Monoclonal antibodies are synthesized by mouse B cells, but with genetic engineering, the mouse derived antibody can be humanized to reduce risk of adverse immune responses.