The goal of this project is to develop a new method of treatment for human B cell lymphoma. The immunoglobulin made by each malignant B cell tumor (idiotype) is unique and has been proven to be an effective target for specific immune attack. The applicant will conduct human clinical trials in which patients in their first and best remission after standard chemotherapy will be immunized with a vaccine made from the immunoglobulin protein derived from their own tumor. The patients will be observed for immune response and for clinical outcome. The applicant will test the hypothesis that an immune response against the tumor is associated with an improved clinical outcome. Vaccine formulations involving different immunologic adjuvants will be tested. In addition a clinical trial will be performed in which the vaccine will be a naked DNA molecule coding for the idiotypic protein. Animal models of B-cell lymphoma will be used to develop more powerful methods of vaccination against the idiotype and to study the mechanisms of tumor immunity. Specifically, the applicant will study the additive effects of immunostimulatory molecules fused onto the DNA or protein vaccines. Viral vectors will be developed for the introduction of immunoglobulin genes into dendritic cells, which in turn will be tested for vaccine potency. Finally, vaccine methods will be optimized for the induction of cytotoxic T cell responses against the tumor cells.
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