TPD52: A Novel Vaccine Target for Prostate Cancer
Annual rept. 1 Sep 2009-31 Aug 2010
TEXAS TECH UNIV HEALTH SCIENCES CENTER LUBBOCK
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The overall goal of this Award is to test the efficacy of TPD52-based vaccines in the TRAMP murine model of prostate cancer, and to characterize vaccine induced mechanisms of tumor immunity. We have continued our evaluation of the ability of TPD52-DNA andor TPD52-protein based vaccines to induce immune responses capable of rejecting the formation of subcutaneous tumors following challenge with prostate-derived TRAMP-C1 or TRAMP-C2 tumor cells. Over the past 12 months we have made the following significant findings or accomplishments First, DNA vaccines encoding the human TPD25 hD52 induced increased protection from not only primary challenge, but secondary challenge with a distinct TRAMP-C tumor, compared to murine TPD52 mD52-DNA based vaccines suggesting the hD52 xeno-antigen was capable of inducing more effective memory responses. Second, the cytokine profile from vaccine induced T cells indicated a cellular Th1-type response that was important for tumor protection. Third, in vivo inhibition of TGF -1 with TPD52-protein vaccination increased protection from tumor challenge demonstrating a regulatory role for TGF -1. Finally, T cell cytokine analyses revealed the presence of a population of CD8 MHC-I-restricted T cells that secrete IL-10 in an antigen-specific manner, suggesting a novel role for CD8 Treg cells in suppressing TPD52-based vaccination in our model.
- Medicine and Medical Research