Critical analysis of an oncolytic herpesvirus encoding granulocyte-macrophage colony stimulating factor for the treatment of malignant melanoma
Tasha Hughes,1 Robert S Coffin,2 Caroline E Lilley,2 Rafael Ponce,2 Howard L Kaufman1
1Departments of General Surgery and Immunology and Microbiology, Rush University Medical Center, Chicago IL, 2BioVex, Inc, a subsidiary of Amgen, Inc, Sherman Oaks, CA, USA
Abstract: Oncolytic viruses that selectively lyse tumor cells with minimal damage to normal cells are a new area of therapeutic development in oncology. An attenuated herpesvirus encoding the granulocyte-macrophage colony stimulating factor (GM-CSF), known as talimogene laherparepvec (T-VEC), has been identified as an attractive oncolytic virus for cancer therapy based on preclinical tumor studies and results from early-phase clinical trials and a large randomized Phase III study in melanoma. In this review, we discuss the basic biology of T-VEC, describe the role of GM-CSF as an immune adjuvant, summarize the preclinical data, and report the outcomes of published clinical trials using T-VEC. The emerging data suggest that T-VEC is a safe and potentially effective antitumor therapy in malignant melanoma and represents the first oncolytic virus to demonstrate therapeutic activity against human cancer in a randomized, controlled Phase III study.
Keywords: granulocyte-macrophage colony stimulating factor, herpesvirus, melanoma, oncolytic virus, treatment
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