Development and applications of oncolytic Maraba virus vaccines

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...

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Bibliographic Details
Published in:Oncolytic virotherapy 2018-01, Vol.7, p.117-128
Main Authors: Pol, Jonathan G, Atherton, Matthew J, Bridle, Byram W, Stephenson, Kyle B, Le Boeuf, Fabrice, Hummel, Jeff L, Martin, Chantal G, Pomoransky, Julia, Breitbach, Caroline J, Diallo, Jean-Simon, Stojdl, David F, Bell, John C, Wan, Yonghong, Lichty, Brian D
Format: Article
Language:English
Subjects:
Advertising executives
Antigens
Beef cattle
Cancer
Cancer vaccines
Clinical trials
Immunology
Immunotherapy
Life Sciences
Oncolytic viral therapy
Ovarian cancer
Primates
Review
T cells
Tumors
Vaccination
Vaccines
Vaccinology
Viruses
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Summary: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.
ISSN:2253-1572
2253-1572
DOI:10.2147/OV.S154494