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Monoclonal Antibodies By Groups C & D Mono vs. Poly Monoclonal Antibodies: Arise from a single clone of cells Homogenous Eg. Antibodies to a plasma cell tumor (myeloma) Polyclonal Antibodies: Formed by several different clones of plasma cells Heterogeneous Arise in an animal in response to typical antigens Monoclonal Antibodies Can be synthesized in the laboratory. Done by fusing a myeloma cell with an antibody-producing cell. These are referred to as hybridomas. Hybridomas can be produce monoclonal antibodies against the antigen of interest in large quantities. How Hybridoma Cells Are Made An animal egg (a mouse) is immunized with the antigen of interest. 2) Spleen cells from this animal are grown in a culture dish in the presence of mouse myeloma cells. 1) - - Myeloma cells grow indefinitely in culture, they do not produce immunoglobulins, and are seen as “immortal” since they are cancerous. Spleen cells supply HGPRT, which the myeloma cells lack, in order to synthesize purines using an external source of Hypoxanthine. Cont’d. 3) Fusion of the cells is encouraged by adding certain chemicals (polyethylene glycol). 4) The cells are grown in a special culture medium (HAT medium) that supports the growth of the fused, hybrid cells but not of the “parental” cells. It is called HAT because it contains Hypoxanthine, Aminopterin, and Thymidine. 5) The resulting clones of the cells are screened for the production of antibody to the antigen of interest Summary of Hybridoma Production Chimeric Monoclonal Antibodies Consists of mouse variable regions and human constant regions. They are being used in the treatment of human diseases like leukemia. Advantages of human constant chain are that human complement are activated and that antibodies against the monoclonal antibody are not formed. Cont’d. Both would not hold true is the constant region was mouse- derived. Advantage of the mouse variable region is that it is much easier to obtain monoclonal antibodies against, for example, a human tumor antigen by inoculating a mouse with the tumor cells. Cont’d. Chimeric antibodies can kill tumor cells either by complement-mediated cytotoxicity or by delivering toxins, for example, diphtheria toxin, specifically to the tumor cell. Clinical Use Monoclonal antibodies are now used in a variety of clinical situations, such as immunosuppression related to organ transplants, treatment of autoimmune disease, treatment of cancer, and the prevention of infectious disease. Examples of MABs Transplant-related immunosuppresion: Basiliximab, Daclizumab, and Muromonab Targets are IL-2 receptor and CD3 on T cells Prevent or treat allograft rejection and graft-versus-host reaction Treatment of autoimmune disease: Infliximab, Adalimumab, and Natalizumab They target Tumor necrosis factor-α and α-integrin Treat rheumatoid arthritis, multiple sclerosis, and Crohn’s disease Cont’d. Prevention of infectious disease: Palivizumab Target is fusion protein of respiratory syncytial virus Prevent pneumonia in susceptible neonates Treatment of cancer: Rituximab, Trastuzumab They target CD20 protein on B cells and epidermal growth factor receptor Treat non-Hodgkins lymphoma and breast cancer respectively Thank You Very Much!
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