Prostate cancer is one of the most prevalent cancers in men. Replication-competent oncolytic herpes simplex virus (oHSV) vectors are a powerful anti-tumor therapy that can exert at least two effects: direct cytocidal activity that selectively kills cancer cells and induction of anti-tumor immunity. In addition, oHSV vectors can also function as a platform to deliver transgenes of interest. In these studies, we have examined the expression of a xenogeneic homologue of the prostate cancer antigen, prostatic acid phosphatase (PAP), with the goal of enhancing virotherapy against PAP-expressing tumors. PAP has already been used for cancer vaccination in prostate cancer patients. Here we show that treatment with oHSV bPΔ6 expressing xenogeneic human PAP (hPAP) significantly reduces tumor growth and increases survival of C57/BL6 mice bearing mouse TRAMP-C2 prostate tumors, whereas expression of syngeneic mouse PAP (mPAP) from the same oHSV vector did not enhance anti-tumor activity. Treatment of mice bearing metastatic TRAMP-C2 lung tumors with oHSV expressing hPAP resulted in fewer tumor nodules. To our knowledge, this is the first report of oncolytic viruses being used to express xenoantigens. This data lends support to the concept of combining oncolytic and immunogenic therapies as a way to improve therapy of metastatic prostate cancer.

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