Sivanandam Venkatesh, LaRocca Christopher J, Chen Nanhai G, Fong Yuman, Warner Susanne G
Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA.
Mol Ther Oncolytics. 2019 Apr 25;13:93-106. doi: 10.1016/j.omto.2019.04.003. eCollection 2019 Jun 28.
Cancer immunotherapy and the emergence of immune checkpoint inhibitors have markedly changed the treatment paradigm for many cancers. They function to disrupt cancer cell evasion of the immune response and activate sustained anti-tumor immunity. Oncolytic viruses have also emerged as an additional therapeutic agent for cancer treatment. These viruses are designed to target and kill tumor cells while leaving the normal cells unharmed. As part of this process, oncolytic virus infection stimulates anti-cancer immune responses that augment the efficacy of checkpoint inhibition. These viruses have the capability of transforming a "cold" tumor microenvironment with few immune effector cells into a "hot" environment with increased immune cell and cytokine infiltration. For this reason, there are multiple ongoing clinical trials that combine oncolytic virotherapy and immune checkpoint inhibitors. This review will detail the key oncolytic viruses in preclinical and clinical studies and highlight the results of their testing with checkpoint inhibitors.
癌症免疫疗法和免疫检查点抑制剂的出现显著改变了许多癌症的治疗模式。它们的作用是破坏癌细胞对免疫反应的逃避并激活持续的抗肿瘤免疫。溶瘤病毒也已成为癌症治疗的另一种治疗剂。这些病毒旨在靶向并杀死肿瘤细胞,同时不损害正常细胞。作为这一过程的一部分,溶瘤病毒感染会刺激抗癌免疫反应,增强检查点抑制的疗效。这些病毒有能力将免疫效应细胞很少的“冷”肿瘤微环境转变为免疫细胞和细胞因子浸润增加的“热”环境。因此,有多项正在进行的临床试验将溶瘤病毒疗法与免疫检查点抑制剂相结合。本综述将详细介绍临床前和临床研究中的关键溶瘤病毒,并突出它们与检查点抑制剂联合测试的结果。