1 National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Centre of Industrial Fermentation, Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, P.R. China.
2 National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control (NIFDC), Beijing, P.R. China.
Hum Gene Ther. 2019 May;30(5):651-660. doi: 10.1089/hum.2018.170. Epub 2019 Jan 16.
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.
溶瘤病毒治疗是一种新的安全治疗策略，基于溶瘤病毒的固有细胞毒性及其以选择性方式在肿瘤内复制和传播的能力。在之前的一项研究中，构建了一种新型的溶瘤单纯疱疹病毒 2（oHSV-2，命名为 OH2）来治疗人类癌症。该研究表明，OH2 在遗传和生物学上是稳定的。即使病毒传代超过 20 代，其抗肿瘤活性仍得以维持。为了将 OH2 推进临床试验，进行了系统的临床前安全性评估，包括：OH2 在 BALB/c 小鼠中的急性毒性试验；OH2 在 BALB/c 小鼠和食蟹猴中的重复剂量毒性试验；以及 OH2 在 BALB/c 小鼠、荷瘤小鼠、荷瘤裸鼠和食蟹猴中的生物分布试验。OH2 的临床前安全性评估结果表明，OH2 是安全的，适合临床试验。
