Kaufman Howard L, Kohlhapp Frederick J, Zloza Andrew
Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, Room 2004, New Brunswick, New Jersey 08901, USA.
Nat Rev Drug Discov. 2015 Sep;14(9):642-62. doi: 10.1038/nrd4663.
Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumour cell killing and the induction of systemic anti-tumour immunity. The molecular and cellular mechanisms of action are not fully elucidated but are likely to depend on viral replication within transformed cells, induction of primary cell death, interaction with tumour cell antiviral elements and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been developed as oncolytic agents, and the approval of the first oncolytic virus by the US Food and Drug Administration (FDA) is anticipated in the near future. This Review provides a comprehensive overview of the basic biology supporting oncolytic viruses as cancer therapeutic agents, describes oncolytic viruses in advanced clinical trials and discusses the unique challenges in the development of oncolytic viruses as a new class of drugs for the treatment of cancer.
溶瘤病毒是一类新型治疗药物,通过双重作用机制发挥抗肿瘤作用,该机制依赖于选择性杀伤肿瘤细胞和诱导全身性抗肿瘤免疫。其分子和细胞作用机制尚未完全阐明,但可能取决于病毒在转化细胞内的复制、原发性细胞死亡的诱导、与肿瘤细胞抗病毒元件的相互作用以及先天性和适应性抗肿瘤免疫的启动。多种天然和基因改造病毒已被开发为溶瘤药物,预计美国食品药品监督管理局(FDA)将在不久的将来批准首个溶瘤病毒。本综述全面概述了支持溶瘤病毒作为癌症治疗药物的基础生物学,描述了处于晚期临床试验阶段的溶瘤病毒,并讨论了将溶瘤病毒开发为一类新型抗癌药物所面临的独特挑战。