Antitumor effects of telomerase-specific replication-selective oncolytic viruses for adenoid cystic carcinoma cell lines.
We evaluated the antitumor effect of a telomerase-specific replication-selective adenovirus (Telomelysin, OBP-301) for adenoid cystic carcinoma (ACC) in vitro and in vivo. Adenovirus E1 gene expression was controlled by human telomerase reverse transcription (hTERT). Infection of ACC cells by OBP-301 induced high E1A mRNA expression and subsequent oncolytic cell death in a dose-dependent manner. Using OBP-401 (TelomeScan), a genetically engineered adenovirus that carries the GFP gene under the control of the cytomegalovirus (CMV) promoter at the deleted E3 region of OBP-301, ACC cells expressed bright GFP fluorescence as early as 12 h after OBP-401 infection. The fluorescence intensity gradually increased in a time-dependent manner, followed by rapid cell death due to the cytopathic effect of OBP-401, as evidenced by the floating, highly light-refractive cells using phase-contrast microscopy. Effects of intratumorally injected OBP-401 against established Acc2 xenograft tumors were seen in BALB/c nu/nu mice. The levels of GFP expression following ex vivo infection of OBP-401 may be of value as a positive predictive marker for the outcome of telomerase-specific virotherapy. Our data clearly indicated that telomerase-specific oncolytic adenoviruses have significant therapeutic potential against human ACC in vitro and in vivo. These results suggest that treatment with OBP-301 and OBP-401 may improve the quality of life of oral cancer patients.
Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ota-ku, Tokyo 145-8515, Japan.
Daisuke
D
Sato
Yuji
Y
Kurihara
Seiji
S
Kondo
Tatsuo
T
Shirota
Yasuo
Y
Urata
Toshiyoshi
T
Fujiwara
Satoru
S
Shintani
D017498:Adenovirus E1 Proteins / Q000235:genetics; D000818:Animals; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D049452:Green Fluorescent Proteins; D006801:Humans; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D017498:Adenovirus E1 Proteins; D049452:Green Fluorescent Proteins; C509186:TERT protein, human; D019098:Telomerase