溶瘤病毒
生物
溶瘤腺病毒
端粒酶逆转录酶
端粒酶
腺病毒科
遗传增强
病毒载体
分子生物学
癌症研究
溶癌病毒
流式细胞术
腺病毒感染
病毒学
病毒
基因
重组DNA
生物化学
作者
Tsuyoshi Sasaki,Hiroshi Tazawa,Joe Hasei,Shuhei Osaki,Toshiyuki Kunisada,Aki Yoshida,Yuichi Hashimoto,Shuya Yano,Ryuichi Yoshida,Shunsuke Kagawa,Futoshi Uno,Yasuo Urata,Toshifumi Ozaki,Toshiya Fujiwara
出处
期刊:Gene Therapy
[Springer Nature]
日期:2012-01-12
卷期号:20 (1): 112-118
被引量:8
摘要
Adenovirus serotype 5 (Ad5) is frequently used as an effective vector for induction of therapeutic transgenes in cancer gene therapy or of tumor cell lysis in oncolytic virotherapy. Ad5 can infect target cells through binding with the coxsackie and adenovirus receptor (CAR). Thus, the infectious ability of Ad5-based vectors depends on the CAR expression level in target cells. There are conventional methods to evaluate the CAR expression level in human target cells, including flow cytometry, western blotting and immunohistochemistry. Here, we show a simple system for detection and assessment of functional CAR expression in human tumor cells, using the green fluorescent protein (GFP)-expressing telomerase-specific replication-competent adenovirus OBP-401. OBP-401 infection induced detectable GFP expression in CAR-expressing tumor cells, but not in CAR-negative tumor cells, nor in CAR-positive normal fibroblasts, 24 h after infection. OBP-401-mediated GFP expression was significantly associated with CAR expression in tumor cells. OBP-401 infection detected tumor cells with low CAR expression more efficiently than conventional methods. OBP-401 also distinguished CAR-positive tumor tissues from CAR-negative tumor and normal tissues in biopsy samples. These results suggest that GFP-expressing telomerase-specific replication-competent adenovirus is a very potent diagnostic tool for assessment of functional CAR expression in tumor cells for Ad5-based antitumor therapy.
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