Characterization of T cell responses specific for a self-antigen expressed in the mouse prostate (40.23)

Abstract

Abstract OBJECTIVE: Examine if functional prostate-specific T cells exist in mice and determine if such T cells might be harnessed for prostate cancer therapy. METHODS: Studies were performed in transgenic mice (POET) expressing ovalbumin (OVA) under control of a prostate-specific promoter and double transgenic POETxOTI and POETxOTII mice, which contain OVA-specific CD8 or CD4 T cells, respectively. RESULTS: Double transgenic mice revealed incomplete central deletion of OTI and OTII cells, with functional prostate-specific T cells still present in the periphery. To model the fate of prostate-specific T cells in which the self-protein is not expressed during development, we transferred OTI or OTII cells into POET mice. While most transferred OTI cells were deleted, the persisting OTI cells were antigen experienced and capable of expanding and inducing prostate inflammation. Transferred OTII cells by contrast maintained a naïve and responsive phenotype. CONCLUSIONS: Antigen experienced prostate-specific CD8 T cells persist, can be induced to expand and infiltrate the normal prostate, and thus may prove useful for cancer therapy. CD4 T cells specific for the same prostate antigen remain naïve, suggesting limited presentation by APC. We are generating TRAMPxPOET mice, which develop OVA-expressing prostate cancer, to study targeting self-antigens for tumor therapy. Supported by the NCI & a CRI Predoctoral Fellowship