Breaking the barriers in cancer care: The next generation of herpes simplex virus-based oncolytic immunotherapies for cancer treatment.

Since the US Food and Drug Administration first approved talimogene laherparepvec for the treatment of melanoma in 2015, the field of oncolytic immunotherapy (OI) has rapidly evolved. There are numerous ongoing clinical studies assessing the clinical activity of OIs across a wide range of tumor types. Further understanding of the mechanisms underlying the anti-tumor immune response has led to the development of OIs with improved immune-mediated preclinical efficacy. In this review, we discuss the key approaches for developing the next generation of herpes simplex virus-based OIs. Modifications to the viral genome and incorporation of transgenes to promote safety, tumor-selective replication, and immune stimulation are reviewed. We also review the advantages and disadvantages of intratumoral versus intravenous administration, summarize clinical evidence supporting the use of OIs as a strategy to overcome resistance to immune checkpoint blockade, and consider emerging opportunities to improve OI efficacy in the combination setting.

Informations de copyright

© 2023 The Author(s).

Déclaration de conflit d'intérêts

N.I.K. reports receipt of institutional research funds from Bristol Myers Squibb, Celgene, GlaxoSmithKline, HUYA Biopharmaceuticals, Merck, Modulation Therapeutics, Novartis, Regeneron, and Replimune, Inc.; personal fees for participation in advisory boards, data safety monitoring committees, or study steering committees from AstraZeneca, Bristol Myers Squibb, Castle Biosciences, Genzyme, Incyte, Iovance, HUYA Biopharmaceuticals, Instil Bio, Merck, Nektar, Novartis, NCCN (from Pfizer), Regeneron, and Replimune, Inc.; travel support from Regeneron; and common stock holdings in Amarin Corp., Asensus Surgical, and Bellicum Pharmaceuticals. K.J.H. reports receipt of research funding or grants from AstraZeneca, Boehringer-Ingelheim, MSD, and Replimune, Inc.; receipt of consulting fees from Arch Oncology, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Codiak, Eisai, Inzen, Merck-Serono, MSD, Oncolys, Pfizer, PsiVac, and Replimune, Inc.; receipt of honoraria from Bristol Myers Squibb, Merck-Serono, and MSD; and participation in data safety monitoring boards or advisory boards for Arch Oncology, AstraZeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Merck-Serono, MSD, Oncolys, Pfizer, PsiVac, and Replimune, Inc. A.M. reports receipt of research funding or grants from AstraZeneca and Bristol Myers Squibb and receipt of consulting fees/honoraria from Amgen, Bristol Myers Squibb, Merck-Serono, Theolytics, and Turnstone Biologics. P.K.B. is an employee and shareholder of Replimune, Inc. D.Z. reports institutional grants from Merck, Genentech, AstraZeneca, Plexxikon, and Synthekine and personal fees from Agenus, Genentech, AstraZeneca, Xencor, Memgen, Takeda, Synthekine, Immunos, Tessa Therapeutics, and Calidi Biotherapeutics.