1. Development and applications of oncolytic Maraba virus vaccines
- Author
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Pol JG, Atherton MJ, Bridle BW, Stephenson KB, Le Boeuf F, Hummel JL, Martin CG, Pomoransky J, Breitbach CJ, Diallo JS, Stojdl DF, Bell JC, Wan Y, and Lichty BD
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MAGE-A3 ,Maraba MG1 ,cancer vaccine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,lcsh:RC254-282 ,tumor antigen ,oncolytic virus - Abstract
Jonathan G Pol,1–5 Matthew J Atherton,6 Byram W Bridle,7 Kyle B Stephenson,8 Fabrice Le Boeuf,9,10 Jeff L Hummel,6,11 Chantal G Martin,8 Julia Pomoransky,8 Caroline J Breitbach,8 Jean-Simon Diallo,9,10 David F Stojdl,8,12 John C Bell,8–10 Yonghong Wan,6 Brian D Lichty6,8 1Gustave Roussy Comprehensive Cancer Institute, Villejuif, France; 2Institut National de la Santé Et de la Recherche Médicale (INSERM), U1138, Paris, France; 3Team 11 labelled Ligue Nationale contre le Cancer, Cordeliers Research Center, Paris, France; 4Université Paris Descartes/Paris V, Sorbonne Paris Cité, Paris, France; 5Sorbonne Universités/Université Pierre et Marie Curie/Paris VI, Paris, France; 6Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada; 7Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada; 8Turnstone Biologics, Ottawa, ON, Canada; 9Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada; 10Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada; 11Clinical Trial Division, CANSWERS, Georgetown, ON, Canada; 12Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada Abstract: Oncolytic activity of the MG1 strain of the Maraba vesiculovirus has proven efficacy in numerous preclinical cancer models, and relied not only on a direct cytotoxicity but also on the induction of both innate and adaptive antitumor immunity. To further expand tumor-specific T-cell effector and long-lasting memory compartments, we introduced the MG1 virus in a prime-boost cancer vaccine strategy. To this aim, a replication-incompetent adenoviral [Ad] vector together with the oncolytic MG1 have each been armed with a transgene expressing a same tumor antigen. Immune priming with the Ad vaccine subsequently boosted with the MG1 vaccine mounted tumor-specific responses of remarkable magnitude, which significantly prolonged survival in various murine cancer models. Based on these promising results, we validated the safety profile of the Ad:MG1 oncolytic vaccination strategy in nonhuman primates and initiated clinical investigations in cancer patients. Two clinical trials are currently under way (NCT02285816; NCT02879760). The present review will recapitulate the discoveries that led to the development of MG1 oncolytic vaccines from bench to bedside. Keywords: Maraba MG1, oncolytic virus, tumor antigen, cancer vaccine, MAGE-A3
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- 2018