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Development and applications of oncolytic Maraba virus vaccines

Authors 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, Lichty BD

Received 30 July 2018

Accepted for publication 18 October 2018

Published 26 November 2018 Volume 2018:7 Pages 117—128


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Chae-Ok Yun

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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