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Determination of Patients' Breast Tumor-Specific Immunity and Its Enhancement with In Vitro Stimulation and Gene Therapy

Abstract : We have made substantial progress in the characterization of a new pre-clinical model system for the growth of patients' breast carcinoma which is now being used by our group for the study of breast tumor-specific immunity. During the past year, we have successfully grown over 40 different patients' breast carcinomas in a SCID mouse system. These tumors have grown with remarkably different histologies and growth rates; these differences are probably reflection of the biological properties of the original tumors. Importantly, we have observed metastatic spread of several of these tumors within the SCID mouse making this model highly relevant to the most critical issues in the study of human breast cancer. We are characterizing these tumors for HER-2/neu expression and for DNA content using flow cytometry and are comparing this data to the same analysis conducted on the original patient's tumor. We have also observed the presence within the tumor-bearing SCID mouse of human tumor infiltrating lymphocytes that have apparently co-engrafted the SCID mouse along with the tumor. We are characterizing these lymphocytes for their surface phenotype and have noticed several mice in which there is a great expansion of these TIL. Most often, thes cells are CD8 positive T cells, but we have also observed a large number of plasma cells and CD4 positive T cells. Thes data indicate that this new mouse model system for the growth of primary human breast carcinoma is a viable one with which preclinical studies directed toward immunotherapy can finally be conducted. During the upcoming year of this proposal, we will develop and test new strategies to enhance the anti-tumor activity of the human tumor-infiltrating lymphocytes we have observed. An abstract, manuscript and additional unexpected findings have been generated a a result of work during the first year.