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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2008; 14(8): 1274-1279
Published online Feb 28, 2008. doi: 10.3748/wjg.14.1274
Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma
Yue-Min Li, San-Tai Song, Ze-Fei Jiang, Qi Zhang, Chang-Qing Su, Guo-Qing Liao, Yi-Mei Qu, Guo-Qing Xie, Ming-Ying Li, Fei-Jiao Ge, Qi-Jun Qian
Yue-Min Li, San-Tai Song, Ze-Fei Jiang, Ming-Ying Li, Fei-Jiao Ge, Clinical Cancer Center, Affiliated Hospital, the Academy of Military Medical Sciences, Beijing 100039, China
Qi Zhang, Chang-Qing Su, Qi-Jun Qian, Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Yue-Min Li, Guo-Qing Liao, Yi-Mei Qu, Guo-Qing Xie, Cancer Department, the 2nd Affiliated Hospital, PLA General Hospital, Beijing 100091, China
Correspondence to: Qi-Jun Qian, PhD, Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. qianqj@yahoo.com
Telephone: +86-21-35030677
Fax: +86-21-35030677
Received: April 10, 2007
Revised: December 6, 2007
Published online: February 28, 2008
Abstract

AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma.

METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300.

RESULTS: The replicative multiples in Hep3B and HepGII after 48 h of CNHK300 proliferation were 40 625 and 65 326 fold, respectively, similar to that of wtAd5.. However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ. CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI.

CONCLUSION: CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5), but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

Keywords: Gene therapy, Virus therapy, Replicative adenovirus, Heptocellular carcinoma