PREPARATION OF GENE-VIRAL THERAPEUTIC SYSTEM CNHK200HA AND ITS ANTITUMOR ACTIVITY ON LUNG CANCER

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.

Preparation of gene-viral therapeutic system CNHK200-hA and its antitumor activity on lung cancer

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 E1b55kDa gene was deleted and the whole E1a 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. Biography: WANG Wei-guo (1967-), male, master of medicine, attending physician. Hangzhou 117 Hospital, majors in cancer therapy.