A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent.
Telomerase is a therapeutic target for cancer. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionaly upregulated exclusively in about 90% of cancer cells. Previous studies have demonstrated that hTERT promoter can control the expression of exogenous genes to the telomerase-positive cancer cells, thus hTERT promoter is an excellent candidate for generating cancer-specific oncolytic adenovirus. In this study, we devised a novel oncolytic adenovirus (Ad.TERT) by replacing the normal E1A regulatory elements with hTERT promoter. Ad.TERT displays cancer-specific E1A expression, virus replication and cytolysis in in vitro experiments. In animal experiments, intratumoral administration of Ad.TERT demonstrates potent antitumoral efficacy at least in two xenograft models (Bcap37 and BEL7404). Ad.TERT was targeted by the telomerase activity in cancer cells and has potent antitumoral efficacy in vivo, and since telomerase activity is a wide-ranged tumor marker, Ad.TERT could be a powerful therapeutic agent for a variety of cancers.
Zou
Weiguo
W
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Luo
Chunxia
C
Zhang
Zilai
Z
Liu
Jing
J
Gu
Jingfa
J
Pei
Zifei
Z
Qian
Cheng
C
Liu
Xinyuan
X
D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology*; D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents; D015153:Blotting, Western; D016923:Cell Death; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016297:Mutagenesis, Site-Directed; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D000091402:Prohibitins; D011401:Promoter Regions, Genetic / Q000235:genetics; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C000717331:PHB2 protein, human; C000717333:Phb2 protein, mouse; D000091402:Prohibitins; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse