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

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

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4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2659-2664
Number of pages6
JournalOncology reports
Volume30
Issue number6
DOIs
Publication statusPublished - Dec 1 2013

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Keywords

  • Adenoid cystic carcinoma
  • Antitumor
  • Telomerase
  • Telomerase-specific replication-selective oncolytic viruses

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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