PREPARATION OF GENE-VIRAL THERAPEUTIC SYSTEM CNHK200-HA AND ITS ANTITUMOR ACTIVITY ON LUNG CANCER

作     者：王伟国 马炬明 苏长青 胡慧珍 钱其军 

作者机构：Department of Internal Medicine Hangzhou 117 Hospital Hangzhou 310004 Department of Viral and Gene Therapy Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2006年第18卷第1期

页      面：1-7页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：This work was supported by the NationalNatural Sciences Foundation of China (No.30572149) andthe National "863" High Technology R & D Project ofChina (No. 2003AA216030) 

主　　题：Adenovirus/replicative Gene therapy Antiangiogenesis Lung cancer 

摘      要：Objective： To develop a novel adenoviral vector system, which combines the advantages of the antiangiogenic gene therapy and virus therapy, and to investigate its antitumor activity on lung cancer. Methods： A new kind of viral vector CNHK200, in which the Elb55kDa gene was deleted and the whole Ela gene was preserved, was constructed. Human angiostatin gene Kringle 1-5 （hA） was amplified and inserted into the genome of the replicative virus CNHK200, generating CNHK200-hA. The expression of hA and its effect on lung cancer cell growth in vitro and in vivo were studied. Results： The novel vector system CNHK200-hA, just like the replicative virus ONYX-015, replicated in p53-deficient tumor cells but not in normal cells, and thus specifically killed tumor cells. In in vitro experiment, both CNHK200-hA and the non-replicative virus Ad-hA could kill tumor cells but the latter needed 100 times more MOI to achieve the same level of cell killing. In in vivo experiment, the therapeutic effect of CNHK200-hA on human lung cancer A549 xenografts in nude mice was significantly better than that of Ad-hA or that of ONYX-015. Conclusion： CNHK200-hA, which carries the angiostatin gene, has the advantages of specific tumor targeting, high expression of transgene in tumor cells and potent antitumor activity.