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Preclinical Safety Evaluation of Oncolytic Herpes Simplex Virus Type 2

作者:Yang Wang, Xiaobing Zhou, Zhen Wu, Han Hu, Jing Jin, Yanping Hu, Yuting Dong, Jianwen Zou, Zeyong Mao, Xiaotai Shi, Yan Huo, Jianjun Lyu, Zhizheng Fang, Wen Zhang, Yujie Zhu, Bo Li, Binlei Liu · 发表于:Human Gene Therapy · 年份:2018 · DOI:10.1089/hum.2018.170 · 被引用次数:33 · 研究领域:Virus-based gene therapy research、Herpesvirus Infections and Treatments、CAR-T cell therapy research

Oncolytic virotherapy is a new and safe therapeutic strategy based on the inherent cytotoxicity of oncolytic viruses and their ability to replicate and spread within tumors in a selective manner. In a previous study, a new type of oncolytic herpes simplex virus type 2 (oHSV-2, named OH2) was constructed to treat human cancers. That study demonstrated that OH2 is genetically and biologically stable. Its antitumor activity was maintained, even after passaging the virus for >20 generations. To advance OH2 into a clinical trial, a systematic preclinical safety evaluation was performed, which included: an acute toxicity test of OH2 in BALB/c mice; repeated dose toxicity tests of OH2 in BALB/c mice and cynomolgus monkeys; and biodistribution assays of OH2 in BALB/c mice, tumor-bearing mice, tumor-bearing nude mice, and cynomolgus monkeys. The results of this preclinical safety evaluation of OH2 indicate that OH2 is safe and suitable for clinical trials.