The purpose of these proposed studies will be to develop and characterize the new model system for the adoptive immunotherapy of an established poorly immunogeneic solid tumor in the mouse. The tumors proposed are the methylcholanthrine-induced tumors MCA 105 and 106. These are poorly immunogeneic, non-cross reactive syngeneic tumors in the C57B16 mouse. After appropriate immunization in vivo, spleen cells will be harvested, in vitro-sensitized, and expanded in interleukin-2 (IL-2). Each tumor will serve as specificity control for the other tumor. Using a replica plating technique, clones will be isolated that are either proliferative or highly cytotoxic. Expansion of these clones and eventually adoptive transfer will help characterize the type of cell active in this poorly immunogeneic tumor model. Similarly, using monoclonal antibodies and negative selection, Ly1?+?g and Ly2?+? cells will be obtained and expanded in IL-2, helping to further characterize the cell(s) mediating the response in this model. Utilizing a subdermal tumor model with these same tumors, sequential sacrifice of mice during tumor rejection will be undertaken. A sample of this tumor then will be studied for the histology of the rejection process as well as the cell populations involved in tumor rejection. Utilizing principles and techniques from the above experiments, attempts will be made to study similar systems in the human. Specifically, solid tumors, such as sarcomas, colon, or gastric cancers, will be purified to single cell suspensions. Attempts will then be made utilizing these tumor preparations to sensitize autologous human lymphocytes in mixed lymphocyte tumor interactions. Specific studies will be undertaken to optimize the conditions. Cloning of reactive cells from resected lymph nodes of draining human tumors will also be attempted. Finally, high reactive cells to human tumors will then be expanded to large numbers using IL-2. If the in vitro activity is maintained in these expanded cells, pilot studies (not planned during this grant period) will be undertaken for in vivo administration of these highly reactive cells offering a highly specific, yet systemic, immunotherapy for human cancer. (TA)
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