Oncotarget

Research Papers:

A novel oHSV-1 targeting telomerase reverse transcriptase-positive cancer cells via tumor-specific promoters regulating the expression of ICP4

Wen Zhang, Keli Ge, Qian Zhao, Xiufen Zhuang, Zhenling Deng, Lingling Liu, Jie Li, Yu Zhang, Ying Dong, Youhui Zhang, Shuren Zhang and Binlei Liu _

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Oncotarget. 2015; 6:20345-20355. https://doi.org/10.18632/oncotarget.3884

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Abstract

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.


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