The Evolution, Current Landscape, and Future Prospects of Oncolytic Virotherapy in Melanoma: Talimogene Laherparepvec and Beyond. Cells 2025 Oct 17;14(20)
Date
10/28/2025Pubmed ID
41148835Pubmed Central ID
PMC12563648DOI
10.3390/cells14201620Scopus ID
2-s2.0-105020080741 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Oncolytic viruses represent an emerging class of therapeutic agents that have the potential to transform the care of patients with melanoma. In this narrative review, we describe the evolution of oncolytic virus approaches. We begin by describing early investigations using wild type viruses and then the development of sophisticated Herpes simplex virus 1 (HSV-1) variant constructs such as talimogene laherparepvec (T-VEC) and vusolimogene oderparepvec (Replimune-1, RP1), which incorporate deletions of viral genes and expression of human or synthetic transgenes to promote tumor selectivity, dendritic cell recruitment, antigen presentation, and stimulation of systemic anti-tumor immune responses. We review the status of clinical trials of oncolytic viruses in melanoma, highlight regulatory challenges, and describe important concepts and key remaining questions within the field. While T-VEC remains the only Food and Drug Administration (FDA)-approved oncolytic virus for melanoma treatment, ongoing research focusing on next-generation viral constructs and combination strategies aims to further improve clinical outcomes and expand the applicability of oncolytic virus therapy in melanoma.
Author List
Smestad J, Rieth J, Laux D, Milhem MAuthor
John Smestad PhD, BS, MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBiological Products
Herpesvirus 1, Human
Humans
Melanoma
Oncolytic Virotherapy
Oncolytic Viruses
