TPD52: A Novel Vaccine Target for Prostate Cancer

摘要

Tumor protein D52 (D52) is a novel self-onco-antigen involved in cellular transformation, proliferation and metastasis that is over-expressed in prostate cancer cells. The overall goal of this Award is to test the efficacy of D52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. Due to unforeseen circumstances during this funding period primarily involving the animal vendor and maternity leave for funded personnel we lost over 6 months of productivity. Consequently, we requested and were granted a no cost extension through 8/31/2012. Despite this unfortunate loss of time, over the past 12 months we made the following significant findings: Heterologous prime-boost vaccination induced more than 80% protection from primary tumor challenge the best we have observed thus far, but only 30% protection from secondary challenge about 8 months later. Similarly, if animals were immunized and rested for 8 months before challenge only about 50% were protected from significant tumor growth suggesting that induction of a more durable response may require modulation of peripheral mechanisms of immune suppression as we previously reported. Finally, we demonstrated for the first time in vivo the critical importance of both CD4+ and CD8+ effector T cells in tumor protection following D52 immunization.