Localized
prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced
tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human
tumor antigen-targeted
therapy, which is recognized by T cells or
antibodies. We used data mining of the
Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidate
antigens were screened by
DNA microarrays. Genes were then validated at the
protein level by tissue microarrays, representing various stages of
CaP disease. Of 43 targets identified by CID, 10 showed an overexpression on the
complementary DNA array in CaP
metastases. The RHAMM (CD168) gene, earlier identified by our group as an immunogenic
antigen in acute and chronic
leukemia, also showed highly significant overexpression in CaP
metastases compared with localized disease and
benign prostatic hyperplasia. At the
protein level, RHAMM was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared with benign tissue. High RHAMM expression was associated with clinical parameters known to be linked to better clinical outcome. Patients with high RHAMM expression in the primaries had a significantly lower risk of biochemical failure. The number of viable cells in cell cultures was reduced in blocking experiments using
hormone-sensitive and
hormone-insensitive metastatic CaP cell lines. Acknowledging the proven immunogenic effects of RHAMM in
leukemia, this
antigen is intriguing as a therapeutic target in far-advanced CaP.