Naturally Existing Oncolytic Virus M1 Is Nonpathogenic for the Nonhuman Primates After Multiple Rounds of Repeated Intravenous Injections.
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). To support the incoming clinical trial of intravenous administration of alphavirus M1 to cancer patients, we assessed the safety of M1 in adult nonhuman 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 sex for the present safety study of oncolytic virus M1. In the first round of administration, five experimental macaques were intravenously injected with six times of oncolytic virus M1 (1 × 10(9) pfu/dose) in 1 week, compared with five 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 was also performed to assess the possibility of encephalitis or arthritis. As a result, no clinical, biochemical, immunological, or medical imaging or 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.
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.|2 Department of Nutrition, School of Public Health, Sun Yat-sen University , Guangzhou, China.
Haipeng
H
Zhang
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.|3 Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University , Guangzhou, China.
Yuan
Y
Lin
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Kai
K
Li
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jiankai
J
Liang
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Xiao
X
Xiao
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jing
J
Cai
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Yaqian
Y
Tan
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Fan
F
Xing
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jialuo
J
Mai
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Yuan
Y
Li
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Wenli
W
Chen
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Longxiang
L
Sheng
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jiayu
J
Gu
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Wenbo
W
Zhu
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.|4 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Wei
W
Yin
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Pengxin
P
Qiu
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Xingwen
X
Su
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Bingzheng
B
Lu
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Xuyan
X
Tian
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jinhui
J
Liu
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Wanjun
W
Lu
5 Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, China.
Yunling
Y
Dou
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Yijun
Y
Huang
6 Diagnostic Imaging Department, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou, China.
Bing
B
Hu
6 Diagnostic Imaging Department, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou, China.
Zhuang
Z
Kang
7 Horae Gene Therapy Center, Department of Microbiology and Physiology Systems, University of Massachusetts Medical School , Worcester, Massachusetts.
Guangping
G
Gao
8 Department of Pharmacology and Neurology, Emory University School of Medicine , Atlanta, Georgia.
Zixu
Z
Mao
9 Department of Neurology & Northwestern Brain Tumor Institute, Center for Genetic Medicine, H. Robert Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine , Chicago, Illinois.
Shi-Yuan
SY
Cheng
10 The Laboratory for Hepatology Research, The Third Affiliated Hospital of Sun Yat-sen University , Guangzhou, China.|11 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, Kansas.
Ling
L
Lu
11 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center , Kansas City, Kansas.
Xue-Tao
XT
Bai
7 Horae Gene Therapy Center, Department of Microbiology and Physiology Systems, University of Massachusetts Medical School , Worcester, Massachusetts.
Shoufang
S
Gong
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.|12 Sun Yat-sen University Cancer Center , Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Guangmei
G
Yan
1 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.|13 Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou, China.
Jun
J
Hu
D000524:Alphavirus / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D050504:Oncolytic Viruses / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral