Jonathan G Pol, Matthew J Atherton, Byram W Bridle, Kyle B Stephenson, Fabrice Le Boeuf, Jeff L Hummel, Chantal G Martin, Julia Pomoransky, Caroline J Breitbach, Jean-Simon Diallo, David F Stojdl, John C Bell, Yonghong Wan, Brian D Lichty
{"title":"Development and applications of oncolytic Maraba virus vaccines.","authors":"Jonathan G Pol, Matthew J Atherton, Byram W Bridle, Kyle B Stephenson, Fabrice Le Boeuf, Jeff L Hummel, Chantal G Martin, Julia Pomoransky, Caroline J Breitbach, Jean-Simon Diallo, David F Stojdl, John C Bell, Yonghong Wan, Brian D Lichty","doi":"10.2147/OV.S154494","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19491,"journal":{"name":"Oncolytic Virotherapy","volume":null,"pages":null},"PeriodicalIF":6.7000,"publicationDate":"2018-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/OV.S154494","citationCount":"33","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncolytic Virotherapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/OV.S154494","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 33
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.