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  • Review Article
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Therapy with oncolytic viruses: progress and challenges

Nature Reviews Clinical Oncology volume 20, pages 160–177 (2023)Cite this article

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Abstract

Oncolytic viruses (OVs) are an emerging class of cancer therapeutics that offer the benefits of selective replication in tumour cells, delivery of multiple eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumour immunity, and a tolerable safety profile that largely does not overlap with that of other cancer therapeutics. To date, four OVs and one non-oncolytic virus have been approved for the treatment of cancer globally although talimogene laherparepvec (T-VEC) remains the only widely approved therapy. T-VEC is indicated for the treatment of patients with recurrent melanoma after initial surgery and was initially approved in 2015. An expanding body of data on the clinical experience of patients receiving T-VEC is now becoming available as are data from clinical trials of various other OVs in a range of other cancers. Despite increasing research interest, a better understanding of the underlying biology and pharmacology of OVs is needed to enable the full therapeutic potential of these agents in patients with cancer. In this Review, we summarize the available data and provide guidance on optimizing the use of OVs in clinical practice, with a focus on the clinical experience with T-VEC. We describe data on selected novel OVs that are currently in clinical development, either as monotherapies or as part of combination regimens. We also discuss some of the preclinical, clinical and regulatory hurdles that have thus far limited the development of OVs.

Key points

  • Talimogene laherparepvec (T-VEC) for patients with melanoma is the first widely approved oncolytic virus, and real-world data from the past 7 years have optimized the role of T-VEC, including identifying patients who are most likely to derive benefit.

  • Research involving T-VEC has since been expanded to clinical trials involving patients with other cancers, earlier administration including in the neoadjuvant setting and combination with other therapeutic agents.

  • Three other oncolytic viruses have been approved in one or a few countries; one non-oncolytic virus was FDA approved for non-muscle invasive bladder cancer in December 2022 and other oncolytic viruses are in clinical development for a variety of cancer indications.

  • Novel oncolytic viruses typically have a tolerable safety profile and several have encouraging levels of activity in early phase clinical studies; nonetheless, challenges remain in optimizing appropriate clinical end points, regulatory pathways and clinical logistics.

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Fig. 1: Potential OV combination strategies in clinical development.
Fig. 2: The balance between antiviral and antitumour immunity.
Fig. 3: Biomarker discovery for OVs.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Sophia Z. Shalhout & David M. Miller

  2. Harvard Medical School, Harvard University, Boston, MA, USA

    Sophia Z. Shalhout, David M. Miller, Kevin S. Emerick & Howard L. Kaufman

  3. Department of Dermatology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    David M. Miller

  4. Division of Head and Neck Surgical Oncology, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Kevin S. Emerick & Howard L. Kaufman

  5. Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Howard L. Kaufman

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S.Z.S. and H.L.K. researched data for this manuscript and made a substantial contribution to discussions of content. All authors wrote and edited and/or reviewed this manuscript prior to submission.

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Correspondence to Howard L. Kaufman.

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Competing interests

H.L.K. is an employee of Ankyra Therapeutics and has received honoraria for participating on advisory boards for Castle Biosciences and Marengo Therapeutics. D.M.M. has received honoraria for participating on advisory boards for Checkpoint Therapeutics, EMD Serono, Pfizer, Merck, Regeneron and Sanofi Genzyme. K.S.E. and S.Z.S. report no competing interests.

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Shalhout, S.Z., Miller, D.M., Emerick, K.S. et al. Therapy with oncolytic viruses: progress and challenges. Nat Rev Clin Oncol 20, 160–177 (2023). https://doi.org/10.1038/s41571-022-00719-w

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