Establishment of a geneª²viral therapeutic system CNHK200ª²hA and its antiª²tumor effect on colon cancer

    WANG Weiª²Guo, MA Juª²Ming, HU Huiª²Zhen, SU Changª²Qing, XUE Huiª²Bin, WU Mengª²Chao, QIAN Qiª²Jun

    Digestive Department, PLA 117 Hospital, Hangzhou 310004, China, Viral £¦ Gene Therapy Center, Eastern Hepatobilliary Surgery Institue, Second Military Medical University, Shanghai 200438, China

    ¡¾Abstract¡¿ AIM: To develop a novel geneª²viral therapeutic system CNHK200ª²hA, which combines the advantages of the gene therapy, antiangiogenic therapy and virus therapy, and to observe its effect on colon tumor. METHODS: The antiangiogenic gene, designated human angiostatin (k1ª²5, hA), was inserted into the genome of the replicative and replicationª²defective adenovirus specific for the tumor cells by virus recombination technology. The expression of the antiangiogenic gene of hA(k1ª²5), the inhibitory effect to angiogenesis and the curative effect to colon cancer were observed respectively by tumor study in mice. RESULTS: A new kind of geneª²viral vector system, designated CNHK200ª²hA(k1ª²5), in which the E1b55,000 gene was deleted but the E1a gene of adenovirus was preserved, constructed. The novel vector system possessed the same property as the replicative virus ONYXª²015, replication and proliferation in the P53- tumor cells but not in the normal cells, thus specifically killing the tumor cells. Besides, it carried hA(k1ª²5), further enhancing the effect of antiª²tumor. When carrying the gene of hA(k1ª²5), it introduced the expression of this gene in tumor cells far more effectively than the adenovirus vector employed in the traditional gene therapy. The assay in vivo showed the CNHK200ª²hA(k1ª²5) expressed antiangiogenic gene in HTª²29 cells, inhibited angieogenesis in tumor and killed the HTª²29 cells more effectively than control group. In comparison of the curative effect of the CNHK200ª²hA(k1ª²5) on colon cancer with that of ONYXª²015 and Adª²hA(k1ª²5), the difference was significant. CONCLUSION: CNHK200ª²hAngio(k1ª²5), a novel vector in which the hA is inserted can increase the expression level of hA. It possesses all the advanª²tages of gene therapy, virus therapy, and antiangiogenic therapy, thus further enhancing the curative effect and overcoming such disadvantages as low transfer rate, low expression, lack of target tropism and low antiª²tumor activity. ......