Abstract
Oncolytic viruses derived from herpes simplex virus (HSV) have shown considerable promise as antitumor agents against solid tumors including ovarian cancer. The current group of oncolytic HSVs was constructed exclusively from type 1 HSV. To exploit further the therapeutic potential of replication-selective viruses, we constructed an oncolytic virus from type 2 HSV by deleting the protein kinase domain of the viral ICP10 gene, which targets the activated Ras signaling pathway in tumor cells. In the study reported here, we administered this HSV-2-derived virus intraperitoneally (i.p.) to nude mice bearing metastatic human ovarian tumor xenografts, evaluated its oncolytic activity, and compared with to that of a virus constructed from HSV-1. Two injections of the HSV-2-derived virus (3 × 106 pfu per dose) led to complete eradication of disseminated tumors in the peritoneal cavity in more than 87% of the mice, whereas the HSV-1-based oncolytic virus, administered at the same dose and on the same schedule, eradicated tumor nodules in only 12% of mice (P<0.01). We conclude that i.p. administration of this HSV-2-based oncolytic virus may provide effective treatment for metastatic human ovarian cancer.
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Acknowledgements
We thank Dr Lawrence Stanberry (University of Texas Medical Branch, Galveston, TX) for providing the wild-type HSV-2 strain 186, and John Gilbert for critical reading of this paper. This work was supported in part by a grant from Department of Defense Ovarian Cancer Research Program (DAMD17-03-1-0434).
Grant support: Department of Defense Ovarian Cancer Research Program (DAMD17-03-1-0434).
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Fu, X., Tao, L. & Zhang, X. An oncolytic virus derived from type 2 herpes simplex virus has potent therapeutic effect against metastatic ovarian cancer. Cancer Gene Ther 14, 480–487 (2007). https://doi.org/10.1038/sj.cgt.7701033
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DOI: https://doi.org/10.1038/sj.cgt.7701033
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