title: Oncolytic herpes simplex virus vectors for cancer virotherapy.
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.
authors.affiliation: Molecular Neurosurgery Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Varghese
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Rabkin
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D005818:Genetic Engineering / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000628:therapy* / Q000821:virology; D009928:Organ Specificity; D011355:Prodrugs; D018139:Simplexvirus / Q000235:genetics*; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D011355:Prodrugs