Tnf

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Inhibition of T cellmediated inflammation

Rheumatoid arthritis, Crohn's disease

antibodies against the cytokine tumor necrosis factor (TNF) used to treat rheumatoid arthritis and other inflammatory diseases, antibodies against CD20 for the treatment of B cell leukemias and for depleting B cells in certain autoimmune disorders, antibodies against the type 2 epidermal growth factor receptor to target breast cancer cells, antibodies against vascular endo-thelial growth factor (a cytokine that promotes angio-genesis) in patients with colon cancer, and so on. • Functional analysis of cell surface and secreted molecules. In biologic research, monoclonal antibodies that bind to cell surface molecules and either stimulate or inhibit particular cellular functions are invaluable tools for defining the functions of surface molecules, including receptors for antigens. Monoclonal antibodies are also widely used to purify selected cell populations from complex mixtures to facilitate the study of the properties and functions of these cells.

One of the limitations of monoclonal antibodies for therapy is that these antibodies are most easily produced by immunizing mice, but patients treated with mouse monoclonal antibodies may make antibodies against the mouse Ig, called a human anti-mouse antibody (HAMA) response. These anti-Ig antibodies eliminate the injected monoclonal antibody and can also cause serum sickness. Genetic engineering techniques have been used to expand the usefulness of monoclonal antibodies. The complementary DNAs (cDNAs) that encode the polypep-tide chains of a monoclonal antibody can be isolated from a hybridoma, and these genes can be manipulated in vitro. As discussed before, only small portions of the antibody molecule are responsible for binding to antigen; the remainder of the antibody molecule can be thought of as a framework. This structural organization allows the DNA segments encoding the antigen-binding sites from a mouse monoclonal antibody to be "stitched" into a cDNA encoding a human myeloma protein, creating a hybrid gene. When it is expressed, the resultant hybrid protein, which retains the antigen specificity of the original mouse monoclonal but has the core structure of a human Ig, is referred to as a humanized antibody. Humanized antibodies are far less likely than mouse monoclonals to appear "foreign" in humans and to induce anti-antibody responses.

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