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Effective Gene-Viral Therapy for Telomerase-Positive Cancers by SelectiveReplicative-Competent Adenovirus Combining with Endostatin Gene

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ABSTRACT 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 AdmE. In summary, we provided a more efficient gene-viral therapy strategy by combining oncolysis with antiangiogenesis.
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资源详细信息： 上传用户：gene 加为好友(请先登陆)
文件类型：文章 - PDF文档 PDF文档
文件大小：494KB
资源来源：转载 - CANCER RESEARCH 64, August 1, 2004
上传时间：2007-01-04 16:32:26
资源标签：基因治疗
所属频道：基因治疗
摘要浏览：1383次
研究生特惠套餐 Ad5/F35 CNHK200 | CNHK500
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