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The Evolution, Current Landscape, and Future Prospects of Oncolytic Virotherapy in Melanoma: Talimogene Laherparepvec
John Smestad1,2, John Rieth3, Douglas Laux3
1Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA.
Abstract:
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.
Insights
Oncolytic viruses, including Herpes simplex virus 1 (HSV-1) variants, are advancing melanoma treatment. Ongoing research and combination strategies aim to improve outcomes for this skin cancer.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic viruses are an emerging therapeutic class with significant potential in melanoma treatment.
- Early investigations utilized wild-type viruses, leading to the development of genetically engineered Herpes simplex virus 1 (HSV-1) constructs.
Purpose of the Study:
- To review the evolution of oncolytic virus approaches for melanoma.
- To discuss the current status of clinical trials, regulatory challenges, and future directions in oncolytic virus therapy for melanoma.
Main Methods:
- Narrative review of oncolytic virus development and clinical applications in melanoma.
- Examination of Herpes simplex virus 1 (HSV-1) variants like talimogene laherparepvec (T-VEC) and vusolimogene oderparepvec (RP1).
Main Results:
- Genetically modified HSV-1 variants enhance tumor selectivity, immune cell recruitment, and anti-tumor immune responses.
- Talimogene laherparepvec (T-VEC) is the sole FDA-approved oncolytic virus for melanoma; vusolimogene oderparepvec (RP1) is under investigation.
Conclusions:
- Next-generation oncolytic viruses and combination therapies hold promise for improving melanoma treatment outcomes.
- Further research is needed to address remaining questions and expand the clinical applicability of oncolytic virus therapy.
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