TY - JOUR
T1 - Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers
AU - Lin, Yuan
AU - Zhang, Haipeng
AU - Liang, Jiankai
AU - Li, Kai
AU - Zhu, Wenbo
AU - Fu, Liwu
AU - Wang, Fang
AU - Zheng, Xiaoke
AU - Shi, Huijuan
AU - Wu, Sihan
AU - Xiao, Xiao
AU - Chen, Lijun
AU - Tang, Lipeng
AU - Yan, Min
AU - Yang, Xiaoxiao
AU - Tan, Yaqian
AU - Qiu, Pengxin
AU - Huang, Yijun
AU - Yin, Wei
AU - Su, Xinwen
AU - Hu, Haiyan
AU - Hu, Jun
AU - Yan, Guangmei
PY - 2014/10/21
Y1 - 2014/10/21
N2 - Oncolytic virotherapy is a growing treatment modality that uses replicating viruses as selective antineoplastic agents. Safety and efficacy considerations dictate that an ideal oncolytic agent would discriminate between normal and cancer cells on the basis of common genetic abnormalities in human cancers. Here, we identify a naturally occurring alphavirus (M1) as a novel selective killer targeting zinc-finger antiviral protein (ZAP)-deficient cancer cells. In vitro, in vivo, and ex vivo studies showed potent oncolytic efficacy and high tumor tropism of M1. We showed that the selectivity depends on ZAP deficiency by systematic identification. A large-scale multicenter pathology study using tissue microarrays reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects for M1. Additionally, M1 killed cancer cells by inducing endoplasmic reticulum stress-mediated apoptosis. Our report provides novel insights into potentially personalized cancer therapy using oncolytic viruses.
AB - Oncolytic virotherapy is a growing treatment modality that uses replicating viruses as selective antineoplastic agents. Safety and efficacy considerations dictate that an ideal oncolytic agent would discriminate between normal and cancer cells on the basis of common genetic abnormalities in human cancers. Here, we identify a naturally occurring alphavirus (M1) as a novel selective killer targeting zinc-finger antiviral protein (ZAP)-deficient cancer cells. In vitro, in vivo, and ex vivo studies showed potent oncolytic efficacy and high tumor tropism of M1. We showed that the selectivity depends on ZAP deficiency by systematic identification. A large-scale multicenter pathology study using tissue microarrays reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects for M1. Additionally, M1 killed cancer cells by inducing endoplasmic reticulum stress-mediated apoptosis. Our report provides novel insights into potentially personalized cancer therapy using oncolytic viruses.
KW - Personalized medicine
KW - Translational inhibition
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=84908077930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908077930&partnerID=8YFLogxK
U2 - 10.1073/pnas.1408759111
DO - 10.1073/pnas.1408759111
M3 - Article
C2 - 25288727
AN - SCOPUS:84908077930
SN - 0027-8424
VL - 111
SP - E4504-E4512
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 42
ER -