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Review
. 2018 Nov 26:7:117-128.
doi: 10.2147/OV.S154494. eCollection 2018.

Development and applications of oncolytic Maraba virus vaccines

Jonathan G Pol  1   2   3   4   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   9   10 , Yonghong Wan  6 , Brian D Lichty  6   8
Affiliations
Review

Development and applications of oncolytic Maraba virus vaccines

Jonathan G Pol et al. Oncolytic Virother. .

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: MAGE-A3; Maraba MG1; cancer vaccine; oncolytic virus; tumor antigen.

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Conflict of interest statement

Disclosure JGP was supported by the Seerave Foundation. BDL was supported by the Terry Fox Foundation, the Ontario Institute for Cancer Research, BioCanRx, and Turnstone Biologics. JGP, MJA, BWB, DFS, JCB, and BDL share ownership of patents for cancer vaccination involving oncolytic Maraba MG1. BDL, JCB, and DFS are cofounders, equity holders, and on the Board of Directors of Turn-stone Biologics. KBS, CGM, JP, and CJB are employees of Turnstone Biologics. JLH is the founder and clinical science director of CANSWERS. The authors report no other conflicts of interest in this work.

References

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