Oncolytic herpes simplex virus vectors for cancer virotherapy.
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.
Varghese
Susan
S
Molecular Neurosurgery Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Rabkin
Samuel D
SD
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
D011355:Prodrugs