Potent antitumor-activity after systemic delivery of a doubly fusogenic oncolytic herpes simplex virus against metastatic prostate cancer

BACKGROUND. Although conventional radiation therapy and surgery are potentially curative treatments for organ-confined prostate cancer, there are few effective treatments for metastatic disease. Oncolytic viruses have shown considerable promise for the treatment of solid tumors including prostate cancer. We recently demonstrated that incorporation of a cell membrane fusion capability into an oncolytic herpes simplex virus (HSV) can significantly increase the antitumor potency of the virus. METHODS. We used a mouse model of primary and metastatic human prostate cancer established from PC-3M-Pro4 to evaluate three different types of oncolytic HSVs: non-fusogenic Baco-1, singly fusogenic Synco-2, and doubly fusogenic Synco-2D. RESULTS. Our results show that Synco-2D has greater oncolytic activity than either Baco-1 or Synco-2 virus. Against lung metastases of human prostate cancer xenografts, intravenous administration of Synco-2D had produced a significant reduction of tumor nodules by day 40 post-inoculation as compared with Synco-2 (P < 0.05), Baco-1 (P < 0.01), and PBS control (P < 0.01). CONCLUSIONS. We conclude that the doubly fusogenic Synco-2D is an effective therapeutic agent for human metastatic prostate cancer.