Research Papers:
A novel oHSV1 targeting telomerase reverse transcriptasepositive cancer cells via tumorspecific promoters regulating the expression of ICP4
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Wen Zhang1,*, Keli Ge1,*, Qian Zhao2, Xiufen Zhuang1, Zhenling Deng1, Lingling Liu1, Jie Li1, Yu Zhang1, Ying Dong1, Youhui Zhang1, Shuren Zhang1, Binlei Liu1,3
1Department of Immunology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
2Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
3Hubei University of Technology, Nanhu, Wuchang District, Wuhan 430068, China
*These authors have contributed equally to this work
Correspondence to:
Binlei Liu, e-mail: [email protected]
Shuren Zhang, e-mail: [email protected]
Keywords: oncolytic HSV-1, hTERT, tumor specific, ICP4, oncolytic virotherapy
Received: January 07, 2015 Accepted: April 24, 2015 Published: May 06, 2015
ABSTRACT
Virotherapy is a promising strategy for cancer treatment. Using the human telomerase reverse transcriptase promoter, we developed a novel tumor-selective replication oncolytic HSV-1. Here we showed that oHSV1-hTERT virus was cytopathic in telomerase-positive cancer cell lines but not in telomerase-negative cell lines. In intra-venous injection in mice, oHSV1-hTERT was safer than its parental oHSV1-17+. In human blood cell transduction assays, both viruses transduced few blood cells and the transduction rate for oHSV1-hTERT was even less than that for its parental virus. In vivo, oHSV1-hTERT inhibited growth of tumors and prolong survival in telomerase-positive xenograft tumor models. Therefore, we concluded that this virus may be a safe and effective therapeutic agent for cancer treatment, warranting clinical trials in humans.