Antitumor effects of telomerase-specific replication-selective oncolytic viruses for adenoid cystic carcinoma cell lines

Sato,Daisuke; Kurihara,Yuji; Kondo,Seiji; Shirota,Tatsuo; Urata,Yasuo; Fujiwara,Toshiyoshi; Shintani,Satoru

doi:10.3892/or.2013.2738

Antitumor effects of telomerase-specific replication-selective oncolytic viruses for adenoid cystic carcinoma cell lines

Authors:
- Daisuke Sato
- Yuji Kurihara
- Seiji Kondo
- Tatsuo Shirota
- Yasuo Urata
- Toshiyoshi Fujiwara
- Satoru Shintani
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Affiliations: Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Ota-ku, Tokyo 145-8515, Japan, Oncolys BioPharma, Inc., Minato-ku, Tokyo 106-0032, Japan, Division of Surgical Oncology, Department of Surgery, Okayama University, Graduate School of Medicine and Dentistry, Kita-ku, Okayama 700-8558, Japan
Published online on: September 19, 2013 https://doi.org/10.3892/or.2013.2738
Pages: 2659-2664

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Abstract

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.

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