MONOCLONAL ANTIBODY ANTI-IDIOTYPE TUMOR VACCINES

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The main objective of this project is to develop monoclonal antibody (MoAb) anti- idiotype (anti-Id) tumor vaccines for the treatment of human cancer. The specific aims of this Phase 2 proposal are to develop anti-Id MoAb vaccines that represent internal images of neuroendocrine tumor-associated antigens (TAA) expressed by human melanoma, neuroblastoma and small cell lung carcinomas (SCLC) and by an experimental rat neuroendocrine animal tumor model. We also intend to generate synthetic peptide vaccines corresponding to the internal antigen idiotopes of whole MoAb vaccine preparations. The administration of peptide subunit idiotope vaccines may minimize potential complications associated with repeated immunization of human subjects with whole murine MoAbs. The whole MoAb and peptide anti-Id vaccine preparations will be tested for anti-tumor effects in the animal tumor model and in human subjects. The results of these in vivo studies should identify those anti-Id vaccine preparations best suited for further clinical trials in human subjects during the Phase 3 effort. In contrast to conventionally purified TAA vaccines, MoAb anti-Id preparations can be readily produced in large quantities and may be employed to enhance immune responses to weakly immunogenic TAA determinants, including carbohydrate and lipid moieties. The re- sults of the Phase 2 studies, combined with the inherent advantages of anti-Id vaccine preparations, may lead to the development of novel tumor vaccine products useful in the therapy of human cancers.