SSX antigens as tumor vaccine targets in human sarcoma

The efficacy of current standard therapies for the treatment of sarcoma remains limited. With the aim of identifying target antigens relevant to the development of vaccine-based immunotherapy of sarcoma, we have addressed the relevance of tumor-specific antigens encoded by genes belonging to the SSX family as vaccine targets in sarcoma tumors. Expression of SSX-1 to -5 was analyzed in a collection of sarcoma tumors of diverse histological subtypes and in sarcoma cell lines. We found expression of at least one SSX-encoded antigen in 42% of sarcoma tumors, including 5 of 7 different histological subtypes, and in 50% of sarcoma cell lines. SSX-1 was the most frequently expressed family member, followed by SSX-4, -2 and -5. Expression of SSX-3 was detected in only one sample. Importantly, most SSX positive samples co-expressed more than one family member. In addition, assessment of CD8+ T cell recognition of HLA-A2+ SSX-2+ sarcoma cells showed that the latter were efficiently recognized and lysed by SSX-2-specific CTLs. The results of this study indicate that SSX antigens are relevant targets for the development of vaccine-based immunotherapy of sarcoma and encourage the start of vaccination trials using SSX-derived immunogens in sarcoma patients.