Evaluating the SSX family of cancer-testis antigens as immunological targets for the treatment of prostate cancer

Prostate cancer remains a significant health concern worldwide, and continues to be the most commonly diagnosed and second-leading cause of cancer-related death among American men. While several therapies have been developed showing clinical efficacy in patients with early-stages of prostate cancer, there remains a lack of curative treatments for advanced or metastatic disease. Tumor immunotherapy is one area of research currently being evaluated for the treatment of prostate cancer and gaining increased attention. While several antigen-specific immunotherapeutic vaccines have been evaluated in clinical trials for the treatment of prostate cancer, relatively few robust clinical responses have been demonstrated, highlighting the importance of identifying new and more relevant target antigens. The SSX family of proteins represents an attractive group of target antigens for the immunotherapeutic treatment of prostate cancer, due to their normal expression in immune privileged tissue and their frequent expression in prostate cancer. We have identified that some prostate cancer patients can develop spontaneous immune responses to one dominantly expressed SSX family member, SSX2. We have also shown that different SSX family members can be expressed in prostate cancer cell lines and tissues and this expression is restricted to metastatic disease. We have shown that a DNA plasmid vaccine encoding SSX2 can elicit robust immune responses to two HLA-A2-restricted SSX2 epitopes, p41-49 and p103-111, in immunized HHDII-DR1 mice. CTL from these mice were found to lyse peptide-pulsed target cells and SSX2+ prostate cancer cells ex vivo in an HLA-A2-restricted manner, indicating that SSX2 proteins encode epitopes presented by prostate cancer cells. We have also demonstrated that SSX vaccine efficacy can be enhanced using an altered peptide ligand strategy to increase epitope affinity for MHC class I. Finally, we found that both native and modified SSX2 vaccines can elicit anti-tumor immune responses in terms of a decrease in SSX2-expressing tumor deveopment in HHDII-DR1 mice. These data verify that SSX proteins are attractive targets for the treatment of prostate cancer, and that a DNA vaccine encoding this antigen should be evaluated in clinical trials of patients with advanced prostate cancer or at risk for metastatic disease.