Meyers Daniel E, Wang Amanda A, Thirukkumaran Chandini M, Morris Don G
Department of Oncology, University of Calgary, Calgary, AB, Canada.
Tom Baker Cancer Centre, Calgary, AB, Canada.
Front Oncol. 2017 Jun 6;7:114. doi: 10.3389/fonc.2017.00114. eCollection 2017.
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy. However, due to their ability to elicit specific antitumor immune responses, they are prime candidates to be paired with other immune-modulating strategies in order to optimize therapeutic efficacy. Synergistic strategies to enhance the efficacy of OV include augmenting the host antitumor response through the insertion of therapeutic transgenes such as GM-CSF, utilization of the prime-boost strategy, and combining OV with immune-modulatory drugs such as cyclophosphamide, sunitinib, and immune checkpoint inhibitors. This review provides an overview of these immune-based strategies to improve the clinical efficacy of oncolytic virotherapy.
溶瘤病毒（OV）是一种有望扩大癌症治疗手段范围的策略。为了发挥疗效，它们依赖于两种一般机制：肿瘤特异性感染/细胞杀伤，随后激活宿主的适应性免疫反应。许多溶瘤病毒属已被用于临床试验，最终在2015年美国食品药品监督管理局批准了一种基因工程疱疹病毒——talimogene laherparepvec（T-VEC）。人们普遍认为，溶瘤病毒作为单一疗法的临床疗效有限。然而，由于它们能够引发特异性抗肿瘤免疫反应，因此它们是与其他免疫调节策略联合以优化治疗效果的主要候选者。增强溶瘤病毒疗效的协同策略包括通过插入治疗性转基因（如GM-CSF）来增强宿主抗肿瘤反应、利用初免-加强策略，以及将溶瘤病毒与免疫调节药物（如环磷酰胺、舒尼替尼和免疫检查点抑制剂）联合使用。本综述概述了这些基于免疫的策略，以提高溶瘤病毒疗法的临床疗效。
