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

被引:7
作者
Sato, Daisuke [1 ]
Kurihara, Yuji [1 ]
Kondo, Seiji [1 ]
Shirota, Tatsuo [1 ]
Urata, Yasuo [2 ]
Fujiwara, Toshiyoshi [3 ,4 ]
Shintani, Satoru [1 ]
机构
[1] Showa Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Ota Ku, Tokyo 1458515, Japan
[2] Oncolys BioPharma Inc, Minato Ku, Tokyo 1060032, Japan
[3] Okayama Univ, Grad Sch Med & Dent, Div Surg Oncol, Dept Surg,Kita Ku, Okayama 7008558, Japan
[4] Okayama Univ Hosp, Ctr Gene & Cell Therapy, Kita Ku, Okayama 7008558, Japan
基金
日本学术振兴会;
关键词
antitumor; telomerase; telomerase-specific replication-selective oncolytic viruses; adenoid cystic carcinoma; SALIVARY-GLAND; HUMAN HEAD; ADENOVIRUS; ESTABLISHMENT; VIROTHERAPY; THERAPY; LUNG;
D O I
10.3892/or.2013.2738
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:2659 / 2664
页数:6
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