Development and applications of oncolytic Maraba virus vaccines.

IF 6.7
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
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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.

溶瘤马拉巴病毒疫苗的研制与应用。
马拉巴囊泡病毒MG1株的溶瘤活性已在许多临床前癌症模型中证明有效,并且不仅依赖于直接的细胞毒性,而且依赖于先天和适应性抗肿瘤免疫的诱导。为了进一步扩大肿瘤特异性T细胞效应器和持久记忆区,我们在癌症初始疫苗策略中引入了MG1病毒。为此,复制无能的腺病毒[Ad]载体和溶瘤MG1各自用表达相同肿瘤抗原的转基因武装。Ad疫苗的免疫引发随后用MG1疫苗增强,产生了显著程度的肿瘤特异性反应,这显著延长了各种小鼠癌症模型的存活时间。基于这些有希望的结果,我们在非人类灵长类动物中验证了Ad:MG1溶瘤疫苗接种策略的安全性,并启动了癌症患者的临床研究。目前正在进行两项临床试验(NCT02285816;NCT02879760)。本综述将从试验台到床边概述导致MG1溶瘤疫苗开发的发现。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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