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Ipilimumab is the name of a human antibody molecule that may have therapeutic activity in patients with advanced melanoma. Manufactured by the pharmaceutical company Bristol-Myers Squibb, this antibody is also known as MDX-010. Ipilimumab is made in the laboratory and is a member of the IgG1 class of antibodies. It binds to the anti-cytotoxic T-lymphocyte antigen (CTLA-4) receptor present on the surface of T-lymphocytes in the body. Blocking the CTLA-4 receptor boosts the cellular immune response allowing the patient’s own lymphocytes to mount an attack against the cancer cells.
Melanoma is a form of skin cancer that can metastasize or spread to other tissues. In the early stages of melanoma, surgery is often an effective form of therapy. Once this cancer has spread, it can be difficult to treat with radiation or chemotherapy. Antibody therapy to boost the immune response may be an option for patients suffering from advanced melanoma.
Antibody therapy with ipilimumab takes advantage of the cycle of division or proliferation of cells in the body known as cytotoxic T-lymphocytes. These lymphocytes have the power to attack cancer cells. A protein known as CD28 is present on the surface of T-lymphocytes and this protein binds to other cell types to stimulate cell division. After cell division occurs, CTLA-4 then serves to provide a stop signal so that cell division does not continue unregulated.
Ipilimumab binds to the CTLA-4 molecule and eliminates the stop signal. The T-lymphocytes can then divide, so more of them are available to fight off the cancer cells. This immunotherapy with ipilimumab, either alone or in combination with vaccines, may increase survival times for people with advanced melanoma. Clinical trials with ipilimumab show that this antibody may have antitumor activity against lung and prostate cancers as well as melanoma.
Patients receive ipilimumab intravenously every few weeks. The exact schedule of therapy is determined by the physician and depends on the presence of side effects. Most patients tolerate ipilimumab well but immune-related side effects may develop if the dividing T-lymphocytes begin to affect normal tissues. These side effects may include rashes, diarrhea, or hepatitis. Immune-related side effects can usually be controlled with corticosteroids, while not interfering with the antitumor response.
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