Oncolytic viruses are native or modified viruses that directly kill tumor cells but spare normal tissue and promote host antitumor immunity. Recently, an oncolytic herpes simplex virus (oHSV) type 1–encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrated significant clinical benefit in a randomized phase III clinical trial for patients with advanced melanoma, leading to regulatory approval in 2015. In this review, we provide a general characterization of herpes simplex viruses and discuss methods for vector modification, which can help limit viral pathogenicity and immunogenicity while promoting antitumor immunogenicity. We also provide insight into general strategies for using oHSV agents in tumor immunotherapy regimens for the treatment of cancer and briefly review some of the currently emerging preclinical and clinical data that support an important role for such agents in the treatment of cancer.


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