title: Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy.
abstract: Tumor immunotherapy is emerging as a promising new treatment option for patients with cancer. T-VEC is an intralesional oncolytic virus therapy based on a modified herpes simplex virus type-1. T-VEC selectively targets tumor cells, causing regression in injected lesions and inducing immunologic responses that mediate regression at uninjected/distant sites. In a randomized phase III trial, T-VEC met its primary endpoint of improving the durable response rate vs granulocyte-macrophage colony-stimulating factor in patients with unresectable melanoma. Responses were observed in injected and uninjected regional and visceral lesions. Exploratory analyses suggested survival differences in favor of T-VEC in patients with untreated or stage IIIB/IIIC/IVM1a disease. T-VEC was generally well tolerated, the most common adverse events being flu-like symptoms. Here, we overview recent advances in cancer immunotherapy, focusing on the clinical development of T-VEC, from first-in-human studies and studies in other cancer types, to ongoing combination trials with checkpoint inhibitors.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: a Division of Hematology-Oncology, Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Puzanov
authors.affiliation: b David Geffen School of Medicine , UCLA , Los Angeles , CA , USA.
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.affiliation: c Melanoma Center and the Center for Immuno-Oncology , Dana-Farber Cancer Institute , Boston , MA , USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: d Department of Oncology , Amgen (Europe) GmbH , Zug , Switzerland.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
authors.affiliation: e Department of Oncology , Amgen Inc ., Thousand Oaks , CA , USA.
authors.forename: Swami
authors.initials: S
authors.lastname: Murugappan
authors.affiliation: f Division of Surgical Oncology , Rutgers Cancer Institute of New Jersey , New Brunswick , NJ , USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
mesh_terms: D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008545:Melanoma / Q000473:pathology / Q000628:therapy* / Q000821:virology; D009367:Neoplasm Staging; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: GM-CSF; Immune checkpoint inhibitors; Immunotherapy; Intralesional therapy; Melanoma; Oncolytic virus; Talimogene laherparepvec