Effective gene-viral therapy for telomerase-positive cancers by selective replicative-competent adenovirus combining with endostatin gene

作     者：Zhang Q Nie M Sham J Su C Xue H Chua D Wang W Cui Z liu Y Liu C Jiang M Fang G Liu X Wu M Qian Q 

作者机构：Laboratory of Viral and Gene Therapy Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China 

出 版 物：《第二军医大学学报》 (Academic Journal of Second Military Medical University)

年 卷 期：2005年第26卷第2期

页      面：194-194页

核心收录：

学科分类：10[医学] 

主　　题：gene therapy replicative adenovirus gene transfer nude mice cell line in vitro 

摘      要：Gene-viral therapy, which uses replication-selective transgene-expressing viruses to manage tumors, can exploit the virtues of gene therapy and virotherapy and overcome the limitations of conventional gene therapy. Using a human telomerase reverse transcriptase-targeted replicative adenovirus as an antiangiogenic gene transfer vector to target new angiogenesis and making use of its unrestrained proliferation are completely new concepts in tumor management. CNHK300-mE is a selective replication transgene-expressing adenovirus constructed to carry mouse endostatin gene therapeutically. Infection with CNHK300-mE was associated with selective replication of the adenovirus and production of mouse endostatin in telomerase-positive cancer cells. Endostatin secreted from a human gastric cell line, SGC-7901, infected with CNHK300-mE was significantly higher than that infected with nonreplicative adenovirus Ad-mE in vitro (800±94.7 ng/ml versus 132.9±9.9 ng/ml) and in vivo (610±42 ng/ml versus 126 +/- 13 ng/ml). Embryonic chorioallantoic membrane assay showed that the mouse endostatin secreted by CNHK300-mE inhibited angiogenesis efficiently and also induced distortion of pre-existing vasculature. CNHK300-mE exhibited a superior suppression of xenografts in nude mice compared with CNHK300 and Ad-mE. In summary, we provided a more efficient gene-viral therapy strategy by combining oncolysis with antiangiogenesis.