Rescuing High Avidity T Cells for Prostate Cancer Immunotherapy

摘要

This is the final report on the grant Rescuing high avidity T cells for prostate cancer immunotherapy. The purpose of the grant proposal is to rescuing high avidity tumor-antigen specific T cells that can respond effectively to prostate cancer cells and delay the development of prostate cancer in the TRAMP mouse model. We have proposed three specific aims: (1) Identify the cells in thymus that express peripheral tumor antigen to induce clonal deletion of tumor antigen reactive T cells; (2) Examine whether anti-B7 antibody treatment in TRAMP mice can rescue the tumor-antigen specific T cells that are otherwise deleted; (3) Determine the thymic function in prostate cancer patients undergoing hormonal therapy. In the past funding pedod we have published two papers that identifying specific cell types in thymus that induce clonal deletion of tumor antigen reactive T cells and elucidating the role of costimulatory molecule B7 on T cell early development. We had one paper under revision on the role of B7 on NKT cell development and another manuscript in preparation on the role of B7 in regulatory T cell development. We have generated preliminary data on the treatment with lymphotoxin b receptor fusion protein to rescue the high avidity tumor antigen specific T cells. We have shown that anti-B7 treatment changed the regulatory T cell numbers and increased the survival time of TRAMP mice.