Cancers figure among the leading causes of morbidity and mortality worldwide. The number of new cases is expected to rise by about 70% over the next 2 decades. Development of novel therapeutic agents is urgently needed for clinical cancer therapy. Alphavirus M1 is a Getah like virus isolated from China with a genome of positive single strand RNA. We have previously identified that alphavirus M1 is a naturally existing oncolytic virus with significant anticancer activity against different kinds of cancer (e.g., liver cancer, bladder cancer and colon cancer). In order to support the incoming clinical trial of intravenous (i.v.) administration of alphavirus M1 to cancer patients, we assessed the safety of M1 in adult non-human primates. We previously presented the genome sequencing data of the cynomolgus macaques (Macaca fascicularis), which was demonstrated as an ideal animal species for virus infection study. Therefore, we chose cynomolgus macaques of either gender, for the present safety study of oncolytic virus M1. In the first round of administration, 5 experimental macaques were intravenously injected with 6 times of oncolytic virus M1 (1×109 pfu/dose) in one week, compared with 5 vehicle injected control animals. The last two rounds of injections were further completed in the following months in the same way as the first round. Body weight, temperature, complete blood count, clinical biochemistries, cytokine profiles, lymphocytes subsets, neutralizing antibody and clinical symptoms were closely monitored at different time points. Magnetic resonance imaging (MRI) was also performed to assess the possibility of encephalitis or arthritis. As a result, no clinical, biochemical, immunological, medical imaging and other pathological evidence of toxicity was found during the whole process of the study. Our results in cynomolgus macaques suggested the safety of intravenous administration of oncolytic virus M1 in cancer patients in the future.
Human gene therapy. 2016 Jun 13 [Epub ahead of print]
Haipeng Zhang, Yuan Lin, Kai Li, Jiankai Liang, Xiao Xiao, Jing Cai, Yaqian Tan, Fan Xing, Jialuo Mai, Yuan Li, Wenli Chen, Longxiang Sheng, Jiayu Gu, Wenbo Zhu, Wei Yin, Pengxin Qiu, Xingwen Su, Bingzheng Lu, Xuyan Tian, Jinhui Liu, Wanjun Lu, Yunling Dou, Yijun Huang, Bing Hu, Zhuang Kang, Guangping Gao, Zixu Mao, Shiyuan Cheng, Ling Lu, Xuetao Bai, Shoufang Gong, Guangmei Yan, Jun Hu
Sun Yat-Sen University, 26469, Zhongshan School of Medicine，School of Public Health, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine，School of Public Health, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, guangdong, China ; ., Sun Yat-Sen University, 26469, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, guangdong, China ; ., University of Massachusetts Medical School, Gene Therapy Ctr & Vector Core, Worcester, Massachusetts, United States ; ., Emory University School of Medicine, 12239, Department of Pharmacology, Atlanta, Georgia, United States ; ., Northwestern University Feinberg School of Medicine, 12244, Chicago, Illinois, United States ; ., University of Kansas Medical Center, 21638, Kansas City, Kansas, United States., University of Kansas Medical Center, 21638, Kansas City, Kansas, United States ; ., University of Massachusetts Medical School, Gene Therapy Ctr & Vector Core, Worcester, Massachusetts, United States ; ., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China., Sun Yat-Sen University, 26469, Zhongshan School of Medicine, Guangzhou, guangdong, China ; .