Engineered oncolytic viruses to treat melanoma: where are we now and what comes next?

ABSTRACT

Introduction: Melanoma treatments have evolved rapidly in the past decade and have included the use of intratumoral injections of engineered oncolytic viruses. One such oncolytic virus is talimogene laherparepvec (T-VEC), which is the first approved therapy of its kind for use in recurrent, unresectable stage IIIB-IVM1a melanoma. Additional oncolytic viruses and their uses in combination with other interventions are currently under investigation.

Areas covered: Oncolytic viruses are being evaluated as immunotherapies for a variety of advanced malignancies. In this article, we review T-VEC, the only FDA-approved engineered oncolytic virus, in addition to ongoing research regarding other oncolytic viruses for the treatment of advanced melanomas. Finally, we discuss opportunities to improve these therapies through viral, host, and tumor-related modifications.

Expert opinion: Engineered and naturally oncolytic viruses have demonstrable local and systemic efficacy as immunotherapies in cancer. T-VEC leads the way with improved survival outcomes for unresectable, stage IIIB-IVM1a melanoma as a monotherapy, and is demonstrating superior results in combination with systemic checkpoint inhibitors. Additional viral vectors show acceptable safety profiles and varying degrees of efficacy in targeting melanoma. The indications for use of oncolytic viruses will expand as their efficacy and appropriate usage is better understood in coming years.

KEYWORDS:

• Metastatic melanoma
• oncolytic virus
• T-VEC
• CVA21
• HF10
• immunotherapy
• OBP-301
• JX-594
• pelareorep
• regional therapy

Article highlights

• Oncolytic viral therapy induces local and systemic anticancer effects when used to treat metatstic melanoma.

• T-VEC is the first FDA approved engineered oncolytic virus to demonstrate improved survival for advanced melanomas.

• Additional oncolytic viruses are being studied in melanoma and other malignancies with varying efficacy.

• The indications for use of T-VEC and other oncolytic viruses will expand with completion of trials evaluating their use in the neoadjuvant, adjuvant, and metastatic settings.

• Combination of these therapies with checkpoint inhibitor immunotherapies is showing improved ORRs. The impact on survival has yet to be determined.

This box summarizes key points contained in the article.

Declaration of interest

JS Zager has acted as a consultant, speaker and received research funding for Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.