CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer
Wang, W-guo.; Xue, H-bin.; Su, C-qing.; Cui, Z-fu.; Nie, M-ming.; Sham, J.; Wu, M-chao.; Qian, Q-jun.
Zhonghua Zhong Liu Za Zhi 27(2): 69-72
2005
ISSN/ISBN: 0253-3766 PMID: 15946541 Document Number: 594207
Objective To develop a novel vector system, which combines the advantages of the gene therapy, antiangiogenic therapy and virus therapy, and to observe its effect on lung cancer. Methods Human angiostatin gene hA (k1-5) was inserted into the genome of the replicative virus; specific for the tumor cells by virus recombination technology. The expression of hA (k1-5), its effect on tumor growth in vitro and in vivo were studied. Results A new kind of gene-viral vector system, designated as CNHK200-hA(k1-5), in which the E1b55 000 gene was deleted but the E1a gene of adenovirus preserved, was constructed. The novel vector system possessed the same property as the replicative virus ONYX-015, which replicates in p53(-) tumor cells but not in normal cells, thus specifically kills tumor cells. In vitro, CNHK200-hA and Ad-hA both could kill A549 tumor cells but the latter needed 100 times more MOI to achieve the same amplitude of cell killing. In vivo, the therapeutic effect of CNHK200-hA on human lung cancer A549 xenograft in nude mice was significantly better than that of Ad-hA and that of tumor-replicative virus ONYX-015. Conclusion CNHK200-hA (k1-5), a novel vector is constructed in which the angiostatin gene is inserted into the genome of the replicative adenovirus cytotoxic to p53-negative tumor cells. It has the advantages of specific tumor targeting, high level gene expression in tumor cells, and potent tumoricidal activity.