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首页> 美国政府科技报告 >Potent Oncolytic Herpes Simplex Virus for the Therapy of Advanced Prostate Cancer.
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Potent Oncolytic Herpes Simplex Virus for the Therapy of Advanced Prostate Cancer.

机译：强效溶瘤性单纯疱疹病毒治疗晚期前列腺癌。

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Currently there is no cure for prostate cancer once the disease has spread beyond the gland. As a large percentage of patients have advanced disease at the time of diagnosis or after the conventional therapy fails, new treatment strategies are urgently needed. We proposed to develop a novel virotherapy for prostate cancer during the funding period. Our working hypothesis was that a fusogenic oncolytic virus would induce a widespread syncytia formation (cell- membrane fusion) in tumor tissues, thus significantly enhancing the antitumor effect. We proposed three tasks to test verify this hypothesis. Task I is to initially establish a metastatic prostate cancer model in mice and then to test the potency of antitumor effect of the fusogenic oncolytic HSV. Task 2 is to directly compare the fusogenic oncolytic HSV with a conventional one in vivo for their toxicity. Task 3 is to determine if cell based carriers could function as a delivery vehicle for systemic delivery of the fusogenic oncolytic HSV. Overall these tasks have been largely achieved during the funding period. Specifically, we have demonstrated that the fusogenic oncolytic HSV has a potent antitumor activity against established prostate cancer even after systemic delivery. Additionally, the oncolytic virus also showed an effective therapeutic effect against metastatic prostate cancer, while showing very little toxicity to the experimental animals. The extension of this studies demonstrates that co-administration of fusogenic virotherapy with cyclophosphamide, an approved anticancer chemotherapy drug that also has immunosuppressive activities, can significantly increase the therapeutic effect of virotherapy, possibly by inhibiting the host's innate antiviral activities. These encouraging preclinical results have promoted us to plan for a phase clinical trial of using one of the fusogenic oncolytic HSVs to treat solid tumors including prostate cancer.

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