In this project human malignancies of the B lymphocyte type will be studied, The long range objectives are to develop new therapies for these tumors and to obtain a better understanding of their biology. The focus will be on the cell surface receptor --the immunoglobulin idiotype which Is unique to each malignant cell clone. Monoclonal anti-idiotype antibodies will be prepared and used in therapeutic trials for patients whose disease has been refractory to standard therapy. In patients who have not yet failed standard therapy and are more likely to be immune competent, the immunoglobulin idiotype will be tested as a vaccine. A murine B cell tumors model will be used to perfect active and passive immunotherapy directed against the idiotype protein. The immunoglobulin V region genes will be cloned from the human B cell tumors and, together with the anti-idiotype antibodies, will be used to analyze the genetic heterogeneity of these tumors. The different types of B cell tumors will be compared for their propensity to undergo immunoglobulin gene mutation and the selective effects of be host on these tumor cell populations will be inferred from the types of mutants which survive in vivo. Cell lines established from various types of human B cell malignancies will be used to study the process of immunoglobulin gene mutation in vitro.
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