Virotherapy with a Type 2 Herpes Simplex Virus–Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma

Purpose: We recently constructed an oncolytic virus from type 2 herpes simplex virus (HSV-2) that selectively targets and kills tumor cells with an activated Ras signaling pathway. Designated FusOn-H2, this virus has shown several discrete killing mechanisms. Here, we evaluated the antitumor immune responses after FusOn-H2–mediated virotherapy in a syngeneic murine neuroblastoma model. Experimental Design: We directly injected FusOn-H2 into established tumors and then measured its antitumor effect and the accompanying tumor-specific immune responses. Several oncolytic HSVs constructed from HSV-1 were included in the same experiments for comparisons. Results: Our data show that tumor destruction by FusOn-H2 in vivo induces potent antitumor immune responses in this syngeneic neuroblastoma model. The elicited cellular immunity not only eradicated neuroblastoma cells in vitro but also inhibited the growth of tumors at sites distant from the virus injection site. Moreover, adoptive transfer of splenocytes from mice receiving virotherapy to naïve mice resulted in a measurable antitumor effect. Conclusion: We conclude that the ability of FusOn-H2 to induce tumor-specific cellular immunity expands the oncolytic repertoire of this virus and increases the likelihood that its use in patients would produce significant therapeutic benefits.