Abstract
Oncolytic viruses (OVs) represent a novel class of cancer immunotherapy agents that preferentially infect and kill cancer cells and promote protective antitumor immunity. Furthermore, OVs can be used in combination with established or upcoming immunotherapeutic agents, especially immune checkpoint inhibitors, to efficiently target a wide range of malignancies. The development of OV-based therapy involves three major steps before clinical evaluation: design, production and preclinical testing. OVs can be designed as natural or engineered strains and subsequently selected for their ability to kill a broad spectrum of cancer cells rather than normal, healthy cells. OV selection is further influenced by multiple factors, such as the availability of a specific viral platform, cancer cell permissivity, the need for genetic engineering to render the virus non-pathogenic and/or more effective and logistical considerations around the use of OVs within the laboratory or clinical setting. Selected OVs are then produced and tested for their anticancer potential by using syngeneic, xenograft or humanized preclinical models wherein immunocompromised and immunocompetent setups are used to elucidate their direct oncolytic ability as well as indirect immunotherapeutic potential in vivo. Finally, OVs demonstrating the desired anticancer potential progress toward translation in patients with cancer. This tutorial provides guidelines for the design, production and preclinical testing of OVs, emphasizing considerations specific to OV technology that determine their clinical utility as cancer immunotherapy agents.
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Acknowledgements
S.G. is supported by grants from the CIHR, the Canadian Cancer Society (CCS), the Canada Foundation for Innovation-John R. Evans Leaders Fund (CFI-JELF), Research Nova Scotia (RNS), the Cancer Research Society (CRS) and the Dalhousie Medical Research Foundation (DMRF). V.K. was supported through the Cancer Research Training Program (CRTP) of the Beatrice Hunter Cancer Research Institute (BHCRI). P.K. was funded by the Killam Predoctoral Scholarship. J.G.P. is supported by the Site de Recherche intégrée sur le Cancer (SIRIC) Cancer Research and Personalized Medicine (CARPEM), Institut National du Cancer (INCa), Cancer ITMO (Multi-Organisation Thematic Institute) of the French Alliance for Life Sciences and Health (AVIESAN) and Fondation pour la Recherche Médicale (FRM). G.K. is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; European Research Council Advanced Investigator Grant “ICD-Cancer”, FRM; a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); European Research Council (ICD-Cancer), European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC CARPEM. This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. J.C.B. is supported by the CIHR, the CCS, BioCanRx and the Terry Fox Research Institute (TFRI).
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Conceptualization was performed by S.G., J.G.P., J.C.B. and G.K. Writing and editing was done by S.G., J.G.P., V.K., P.K., M.L.-G., J.C.B. and G.K. Project administration was handled by S.G., J.G.P., J.C.B. and G.K.
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J.G.P. is named as an inventor on patents for cancer vaccination involving an oncolytic rhabdovirus. These patents have been licensed to Turnstone Biologics. G.K. holds research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys and Vascage. G.K. consults for Reithera. G.K. is on the Board of Directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. G.K. is on the scientific advisory boards of Hevolution, Institut Servier and Longevity Vision Funds. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. J.C.B. is a co-founder of Turnstone Biologics and Esphera Synbio. J.C.B. holds multiple patents involving the development of OV-based therapeutics. J.C.B. is on the advisory boards of Transgene, Cytonus, Abalos and hCBioscience.
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Gujar, S., Pol, J.G., Kumar, V. et al. Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy. Nat Protoc (2024). https://doi.org/10.1038/s41596-024-00985-1
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DOI: https://doi.org/10.1038/s41596-024-00985-1
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