Modulation of T Cell Tolerance in a Murine Model for Immunotherapy of Prostatic Adenocarcinoma
Annual rept. 1 Sep 2001-31 Aug 2002
STATE UNIV OF NEW YORK UPSTATE MEDICAL CENTER SYRACUSE
Pagination or Media Count:
The goal of this project is to characterize T cell tolerance to prostate tumor antigens and identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. -We currently use the TRAMP model which is a transgenic mouse line that develops primary prostatic tumors due to expression of the sv4O T antigen TAg under the transcriptional control of a prostate-specific promoter. In this summary, we report that TRAMP mice express TAg in the thymus which indicates that both central and peripheral tolerance exist. We have begun initial studies to characterize tolerance to TAg in TRAMP mice by generating vaccines that express TAg and elicit anti-TAg responses in no-transgenic mice. We have also begun studying the trafficking and activation of TAg-specific T cells transferred into tumor-bearing TRAMP mice. Results from these preliminary studies suggest that naive, tumor antigen-specific T cells undergo initial states of activation and home to the prostate, where the antigen is expressed. Our on-going studies are aimed at understanding the activation state of these T cells after they encounter their cognate antigen in the tumor as well as the effects of androgen ablation on tumor-specific T cell activation.
- Anatomy and Physiology
- Medicine and Medical Research