Rescuing High Avidity T Cells for Prostate Cancer Immunotherapy
Abstract
This is the first annual report on the grant Rescuing high avidity T cells for prostate cancer immunotherapy". The purpose of the grant proposal is to rescue 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. The innovative idea is based on the hypothesis that blockade of the T cell costimulatory pathway in adults will inhibit the deletion of high avidity tumor antigen specific T cells. We have proposed three specific aims in the grant, (I) - 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 period, we have completed the specific aim 1 and obtained promising preliminary data in specific aim 2. Through bone marrow radiation chimera mice experiments that we proposed in specific aim 1, we have shown that expression of the self antigen in thymic epithelial cells is both necessary and sufficient to induce clonal deletion. Surprisingly, while bone marrow-derived peripheral antigen expressing cells failed to induce clonal deletion, they did cause the activation-induced cell death of autoreactive cells in the secondary lymphoid organs. Thus, the BM-derived PAE have a distinct function in the maintenance of tolerance to tissue-specific antigens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427160
Entities
People
- Pan Zheng
Organizations
- Ohio State University