Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma.
OBJECTIVE
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 HepG II after 48 h of CNHK300 proliferation were 40625 and 65326 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.


CONCLUSIONS
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.
Li
Yue-Min
YM
Clinical Cancer Center, Affiliated Hospital, The Academy of Military Medical Sciences, Beijing 100039, China.
Song
San-Tai
ST
Jiang
Ze-Fei
ZF
Zhang
Qi
Q
Su
Chang-Qing
CQ
Liao
Guo-Qing
GQ
Qu
Yi-Mei
YM
Xie
Guo-Qing
GQ
Li
Ming-Ying
MY
Ge
Fei-Jiao
FJ
Qian
Qi-Jun
QJ
D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008856:Microscopy, Fluorescence / Q000379:methods; D050130:Oncolytic Virotherapy / Q000379:methods*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D019098:Telomerase / Q000096:biosynthesis / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014779:Virus Replication
D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D019098:Telomerase; C022616:thiazolyl blue