Abstract A66: Expression and immunotherapeutic targeting of the SSX family of cancer-testis antigens in prostate cancer

Abstract

Abstract Members of the SSX family of proteins were among the first cancer-testis antigens (CTA) identified. Characterized by tissue-restricted expression to MHC class l-deficient germline cells and frequent ectopic expression in tumors of various histological origin, CTA are highly tumor-specific antigens. SSX proteins comprise a family of ten members with mRNA expression often found in advanced-stage disease and associated with worse patient prognosis. We have previously shown that humoral and cell-mediated immune responses to SSX2 can arise spontaneously in patients with prostate cancer, which combined with the expression of these proteins in MHC class l-negative tissue, makes SSX proteins potentially attractive targets for tumor immunotherapy. In the current study, we evaluated SSX family member expression in prostate cancer cell lines and tumor biopsies to identify therapeutic targets for vaccine therapy in prostate cancer. We found by RT-PCR and qRT-PCR that SSX1, SSX2, and SSX5 were frequently expressed in prostate cancer cell lines and could be induced by treatment with epigenetic modifying agents (EMA) such as 5-aza-2′-deoxycytidine. Furthermore, we observed differential SSX protein expression in paraffin-embedded prostate cancer biopsies on tissue microarray by immunohistochemical staining. Interestingly, SSX expression in patient samples was restricted to metastatic prostate cancer lesions (5/22; 23%), while expression in primary prostate tumors was not observed (0/73). Finally, we determined that it is possible to elicit cross-reactive immune responses to a dominant SSX epitope p103–111 shared by the different SSX family members by immunization of A2/DR1 transgenic mice with SSX peptides or a plasmid DNA vaccine encoding SSX2. Overall, these results suggest that multiple SSX family members are expressed in prostate cancer and can be simultaneously targeted using immunotherapeutic vaccines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A66.