Inducible expression of a prostate cancer-testis antigen, SSX-2, following treatment with a DNA methylation inhibitor

BACKGROUND. Active immunotherapies are one approach being developed as novel treatments for prostate cancer. Critical to the success of these therapies is the identification of appropriate target antigens. We have been seeking to identify immunologically recognized proteins, cancer-testis antigens (CTA) in particular, in patients with prostate cancer that would be rational target antigens. METHODS. Using a previously reported panel of 29 different CTA, we used sera from 98 patients with prostate cancer and 50 healthy male blood donor controls to detect CTA-specific IgG. We then further evaluated the expression of one antigen, SSX-2, in prostate cancer cell lines and tissues. RESULTS. We identified IgG specific for NY-ESO-1, LAGE-1, NFX-2, and SSX-2 in at least 1/98 individuals with prostate cancer. We demonstrated that SSX-2 is a prostate CTA, and its expression is associated with metastatic prostate cancer. In addition, we report that the treatment of at least two human prostate cancer cell lines with the DNA methylation inhibitor 5-aza-2'-deoxycytidine induced the expression of SSX-2. In contrast, treatment of a normal prostate epithelial cell line (RWPE-1) with 5-aza-2'-deoxycytidine did not induce SSX-2 expression. CONCLUSIONS. Our findings suggest that SSX-2 could be further pursued as an immunotherapeutic target in prostate cancer, and that treatment with 5-aza-2'-deoxycytidine could be exploited to modulate antigen expression in combination with immunotherapeutic approaches.