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Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer

Cancer Gene Therapy volume 9, pages 935–945 (2002)Cite this article

Abstract

G207 and NV1020 are two replication-competent, multimutant oncolytic herpes simplex viruses evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. Deletion of both γ134.5 genes and inactivation of ICP6 (ribonucleotide reductase) allows G207 to selectively replicate within tumor cells. NV1020 is another attenuated recombinant herpes virus with deletions of the HSV joint region, with deletion of only one copy of the γ134.5 gene, and with the ICP6 gene intact. In vitro, both G207 and NV1020 effectively infected, replicated, and killed human gastric cancer cells, with NV1020 being more effective at lower concentrations of virus. In a murine xenograft model of peritoneally disseminated gastric cancer, both NV1020 and G207 reduced tumor burden when given intraperitoneally (i.p.) at higher doses. When viral doses were lowered or when advanced tumor was treated, i.p. NV1020 was superior to i.p. G207. In vitro viral replication and cytotoxicity predicted the in vivo antitumor response. Intravenous delivery of either G207 or NV1020 failed to reduce tumor burden, demonstrating the importance of regional therapy as treatment for compartmentalized malignancy. Both agents were safe for use in animals, and immunohistochemistry performed on mouse tissue revealed selective viral targeting of tumor. Oncolytic therapy using genetically engineered HSVs represents a promising strategy for peritoneal malignancies.

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Acknowledgements

This work was supported in part by Grants RO1 CA 76416, RO1 CA 72632, and RO1 RO1CA/DK80982 (YF) from the National Institutes of Health, Grant MBC-99366 (YF) from the American Cancer Society, and a grant from the Lustgarten Foundation.

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

    Joseph J Bennett, Keith A Delman, Bryan M Burt, Adam Mariotti, Sandeep Malhotra, Jonathan Zager, Henrik Petrowsky & Yuman Fong

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

    Stephen Mastorides

  3. Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA

    Howard Federoff

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Correspondence to Yuman Fong.

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Bennett, J., Delman, K., Burt, B. et al. Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer. Cancer Gene Ther 9, 935–945 (2002). https://doi.org/10.1038/sj.cgt.7700510

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