Center for Stem Cell Therapeutics and Imaging and.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Clin Invest. 2019 Mar 4;129(4):1407-1418. doi: 10.1172/JCI122287.
Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. In the last two decades, different oncolytic viruses (OVs) have been modified and tested in a number of preclinical studies, some of which have led to clinical trials in cancer patients. These clinical trials have revealed several critical limitations with regard to viral delivery, spread, resistance, and antiviral immunity. Here, we focus on promising research strategies that have been developed to overcome the aforementioned obstacles. Such strategies include engineering OVs to target a broad spectrum of tumor cells while evading the immune system, developing unique delivery mechanisms, combining other immunotherapeutic agents with OVT, and using clinically translatable mouse tumor models to potentially translate OVT more readily into clinical settings.
溶瘤病毒治疗（OVT）是一种很有前途的方法，其中 WT 或工程病毒选择性复制并破坏肿瘤细胞，而不伤害正常细胞。在过去的二十年中，已经对多种溶瘤病毒（OV）进行了修饰和测试，其中一些已经在癌症患者中进行了临床试验。这些临床试验揭示了病毒传递、传播、耐药性和抗病毒免疫方面的几个关键限制。在这里，我们重点介绍了为克服上述障碍而开发的有前途的研究策略。这些策略包括设计针对广泛的肿瘤细胞而逃避免疫系统的 OV，开发独特的传递机制，将其他免疫治疗剂与 OVT 结合，以及使用可临床转化的小鼠肿瘤模型，以便更轻松地将 OVT 转化为临床环境。
