Masemann Dörthe, Boergeling Yvonne, Ludwig Stephan
.
Biol Chem. 2017 Jul 26;398(8):891-909. doi: 10.1515/hsz-2017-0103.
Within recent decades, viruses that specifically target tumor cells have emerged as novel therapeutic agents against cancer. These viruses do not only act via their cell-lytic properties, but also harbor immunostimulatory features to re-direct the tumor microenvironment and stimulate tumor-directed immune responses. Furthermore, oncolytic viruses are considered to be superior to classical cancer therapies due to higher selectivity towards tumor cell destruction and, consequently, less collateral damage of non-transformed healthy tissue. In particular, the field of oncolytic RNA viruses is rapidly developing since these agents possess alternative tumor-targeting strategies compared to established oncolytic DNA viruses. Thus, oncolytic RNA viruses have broadened the field of virotherapy facilitating new strategies to fight cancer. In addition to several naturally occurring oncolytic viruses, genetically modified RNA viruses that are armed to express foreign factors such as immunostimulatory molecules have been successfully tested in early clinical trials showing promising efficacy. This review aims to provide an overview of the most promising RNA viruses in clinical development, to summarize the current knowledge of clinical trials using these viral agents, and to discuss the main issues as well as future perspectives of clinical approaches using oncolytic RNA viruses.
在最近几十年里，专门靶向肿瘤细胞的病毒已成为对抗癌症的新型治疗剂。这些病毒不仅通过其细胞裂解特性发挥作用，还具有免疫刺激特性，可重新引导肿瘤微环境并刺激针对肿瘤的免疫反应。此外，溶瘤病毒由于对肿瘤细胞破坏具有更高的选择性，因此对未转化的健康组织的附带损害较小，被认为优于传统的癌症治疗方法。特别是，溶瘤RNA病毒领域正在迅速发展，因为与已有的溶瘤DNA病毒相比，这些制剂具有替代的肿瘤靶向策略。因此，溶瘤RNA病毒拓宽了病毒治疗领域，为对抗癌症提供了新策略。除了几种天然存在的溶瘤病毒外，经过基因改造以表达诸如免疫刺激分子等外源因子的RNA病毒已在早期临床试验中成功测试，显示出有前景的疗效。本综述旨在概述临床开发中最有前景的RNA病毒，总结使用这些病毒制剂的临床试验的当前知识，并讨论使用溶瘤RNA病毒的临床方法的主要问题以及未来前景。
