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Review Article

Oncolytic herpes simplex virus vectors for cancer virotherapy

Cancer Gene Therapy volume 9, pages 967–978 (2002)Cite this article

Abstract

Oncolytic herpes simplex virus type 1 (HSV-1) vectors are emerging as an effective and powerful therapeutic approach for cancer. Replication-competent HSV-1 vectors with mutations in genes that affect viral replication, neuropathogenicity, and immune evasiveness have been developed and tested for their safety and efficacy in a variety of mouse models. Evidence to-date following administration into the brain attests to their safety, an important observation in light of the neuropathogenicity of the virus. Phase I clinical traits of three vectors, G207, 1716, and NV1020, are either ongoing or completed, with no adverse events attributed to the virus. These and other HSV-1 vectors are effective against a myriad of solid tumors in mice, including glioma, melanoma, breast, prostate, colon, ovarian, and pancreatic cancer. Enhancement of activity was observed when HSV-1 vectors were used in combination with traditional therapies such as radiotherapy and chemotherapy, providing an attractive strategy to pursue in the clinic. Oncolytic HSV-1 vectors expressing “suicide” genes (thymidine kinase, cytosine deaminase, rat cytochrome P450) or immunostimulatory genes (IL-12, GM-CSF, etc.) have been constructed to maximize tumor destruction through multimodal therapeutic mechanisms. Further advances in virus delivery and tumor specificity should improve the likelihood for successful translation to the clinic.

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Acknowledgements

We would like to thank the past and current members of the laboratory who have contributed to this research, in particular RL Martuza and T Todo for their invaluable assistance and insight. SD Rabkin is a member of the Scientific Advisory Board of MediGene, which has a license from Georgetown University for G207 and other vectors. This research has been supported, in part, by grants from the National Institutes of Health (NS32677, NS33342), Department of Defense (DAMD17-99-1-9202, DAMD17-98-1-8490), and CaPCURE Foundation (Santa Monica, CA).

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  1. Molecular Neurosurgery Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, 02129, Massachusetts, USA

    Susan Varghese & Samuel D Rabkin

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  1. Susan Varghese
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  2. Samuel D Rabkin
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Correspondence to Samuel D Rabkin.

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Varghese, S., Rabkin, S. Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther 9, 967–978 (2002). https://doi.org/10.1038/sj.cgt.7700537

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