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Monoclonal Antibodies in the Treatment of Cancer

© David Olle

The term monoclonal antibody means a population of identical antibody-secreting cells derived from a single cell. Monoclonal antibodies are prepared by injecting mice with a specific tumor antigen so that their immune system will make antibodies against this antigen. Since the antibody-secreting B lymphocytes are unstable in culture, they are fused with cells derived from a B lymphocyte tumor. The resulting "hybridoma" cell can reproduce indefinitely in culture, and secretes large quantities of pure antibody.

Since monoclonal antibodies could be directed against a particular type of cancer, they held a great deal of promise. Unfortunately, for the first 20 years their use in treatment was disappointing. The immune systems of the patients recognized the mouse antibodies as foreign antigens and developed antibodies against them. Typically, the monoclonal antibodies could be used only once or twice.

The current picture looks a lot brighter. By means of genetic engineering, so-called chimeric antibodies are prepared that contain both human and mouse sections. The mouse section is located in the variable region of the antibody that contains the antigen- binding site, while the human section is in the constant region. After the variable region binds to the cancer antigen, the human section activates complement and cytotoxic T cells to destroy the cancer cell. There are two chimeric antibodies approved by the Food and Drug Administration for use in treating cancer.

Rituximab (trade name (Rituxan) is a monoclonal antibody that is used against non-Hodgkin's lymphoma. Most lymphomas are of B cell origin and more than 90% of these tumors express the CD20 antigen. Rituximab binds to the CD20 antigen on normal B cells as well as lymphoma cells. Although there is a depletion of normal B cells in the body, it does not result in an increase in infections, and B cell numbers recover following treatment. When Rituximab is used as the sole treatment for patients with slow growing lymphoma, about one-half of the patients show a partial or total remission of the disease. When used with chemotherapy, the response rate can increase to as high as 95%. When patients have a more aggressive lymphoma, patients with smaller tumors have a better response to Rituximab therapy.

Breast cancer patients with a poor prognosis (predicted outcome) often have a genetic defect that causes cancer cells to overproduce a protein called HER-2. This protein is known as a tyrosine kinase receptor, and when activated results in the growth of cancer cells. The monoclonal antibody Trastuzumab (trade name Herceptin) binds to HER-2, preventing its activity. Since Herceptin only works with patients whose cancer is overexpressing HER-2, it is essential to test patients for this protein. It is used in conditions where chemotherapy has failed, or can be used together with chemotherapy.

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