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Coadministration of a Herpes Simplex Virus-2–Based Oncolytic Virus and Cyclophosphamide Produces a Synergistic Antitumor Effect and Enhances Tumor-Specific Immune Responses

¹ Center for Cell and Gene Therapy and Departments of ² Pediatrics and ³ Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas

Requests for reprints: Xiaoliu Zhang, Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: 713-798-1256; Fax: 713-798-1230; E-mail: xzhang{at}bcm.tmc.edu.

Despite their unique property of selective replication and propagation in tumor tissues, oncolytic viruses have had only limited antitumor effects in cancer patients. One of the major reasons is probably the host's immune defense mechanisms, which can restrict the ability of the virus to replicate and spread within tumors. The innate immune system, which can be rapidly activated during virus infection, likely plays a more pivotal antiviral role than does acquired immunity, as the antitumor effect of an oncolytic virus is mainly generated during the acute phase of virus replication. To exploit the potential of cyclophosphamide, a cancer chemotherapeutic drug that also inhibits innate immune responses, to enhance the activity of oncolytic viruses, we evaluated the effect of coadministration of this drug with a herpes simplex virus-2–based oncolytic virus (FusOn-H2) against Lewis lung carcinoma, which is only semipermissive to infection with FusOn-H2. This strategy synergistically enhanced the antitumor effect against lung carcinoma growing in mice. It also potentiated the ability of FusOn-H2 to induce tumor-specific immune responses. Together, our results suggest that coadministration of FusOn-H2 with cyclophosphamide would be a feasible way to enhance the antitumor effects of this oncolytic virus in future clinical trials. [Cancer Res 2007;67(16):7850–5]

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