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lüll Oncolytic herpes simplex virus vectors for cancer virotherapy Varghese S; Rabkin SDCancer Gene Ther 2002[Dec]; 9 (12): 967-78Oncolytic 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.|Animals[MESH]|Clinical Trials as Topic[MESH]|Drug Delivery Systems[MESH]|Genetic Engineering/methods[MESH]|Genetic Therapy/*methods[MESH]|Genetic Vectors/genetics/*pharmacology[MESH]|Humans[MESH]|Mutation[MESH]|Neoplasms/*therapy/virology[MESH]|Organ Specificity[MESH]|Prodrugs[MESH]|Simplexvirus/*genetics[MESH]|Transcription, Genetic[MESH]|Virus Replication[MESH] |