Telomerase-specific oncolytic virotherapy for human cancer with the hTERT promoter.
Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. Telomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. We constructed an attenuated adenovirus 5 vector (Telomelysin, OBP-301), in which the hTERT promoter element drives expression of E1 genes. Telomelysin replicated efficiently and induced marked cell killing in a panel of human cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal human cells lacking telomerase activity. We further modified the E3 region of OBP-301 to contain green fluorescent protein (GFP) gene for monitoring viral replication (TelomeScan, OBP-401). When TelomeScan was intratumorally injected into human tumors orthotopically implanted into the rectum in mice, para-aortic lymph node metastasis could be visualized at laparotomy under a three-chip color cooled charged-coupled device camera. This article reviews recent highlights in this rapidly evolving field: cancer therapeutic and cancer diagnostic approaches using the telomerase-specific oncolytic adenoviruses.
Fujiwara
Toshiyoshi
T
Center for Gene and Cell Therapy, Okayama University Hospital, Department of Surgery, Okayama Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. toshi_f@md.okayama-u.ac.jp
Tanaka
Noriaki
N
D000256:Adenoviridae / Q000235:genetics; D017498:Adenovirus E1 Proteins; D000818:Animals; D017321:Clinical Trials, Phase I as Topic; D005822:Genetic Vectors / Q000627:therapeutic use*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000175:diagnosis / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
D017498:Adenovirus E1 Proteins; D049452:Green Fluorescent Proteins; D019098:Telomerase