Clinical development of talimogene laherparepvec (T-VEC): a modified herpes simplex virus type-1-derived oncolytic immunotherapy

Expert Rev Anticancer Ther. 2015;15(12):1389-403. doi: 10.1586/14737140.2015.1115725.

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.

Keywords: GM-CSF; Immune checkpoint inhibitors; Immunotherapy; Intralesional therapy; Melanoma; Oncolytic virus; Talimogene laherparepvec.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Herpesvirus 1, Human / genetics
  • Humans
  • Immunotherapy / methods*
  • Melanoma / pathology
  • Melanoma / therapy*
  • Melanoma / virology
  • Neoplasm Staging
  • Oncolytic Virotherapy / adverse effects
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses / genetics
  • Randomized Controlled Trials as Topic
  • Skin Neoplasms / pathology
  • Skin Neoplasms / therapy*
  • Skin Neoplasms / virology

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor