Combining Radiotherapy and Immunotherapy to Target Surviving in Prostate Cancer; Annual summary rept. 1 Jan-31 Dec 2007

摘要

Here, we propose to harness the immune system by immunotherapy (IT) alongside conventional radiotherapy (RT) to improve the treatment of men with advanced or recurrent prostate cancer. The overall aim is to determine whether local irradiation of prostate tumors in a preclinical and clinical setting leads to measurable tumor-specific immune responses and whether tumor vaccination can boost these immune responses possibly leading to better tumor control. Survivin is our tumor antigen of choice because it seems superior to other prostate tumor antigens. We generated stable mouse prostate cancer cell lines (TRAMP C1 and TRAMP C2) that express human HLA-A2.1 and we were able to confirm that these cells express survivin. These are two important steps as this will allow us to examine the responses to human surviving epitopes that are clinically relevant within a transgenic humanized mouse model. Enumeration of circulating survivin-specific CD8+ T lymphocytes in prostate cancer patients using tetramers indicated that many patients have higher than normal numbers of these T cells and that they are increased further upon completion of radiation treatment. Whether or not this is due to increase in antigenic peptide liberation and whether this will translate to tumor regression we don't know. What is clear is that RT does not induce immune tolerance to surviving making IT approaches feasible in combination with RT.