[CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer].
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.


CONCLUSIONS
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.
Wang
Wei-guo
WG
Viral & Gene Therapy Center, Eastern Hepatobilliary Surgery Institue, Second Military University, Shanghai 200438, China. wangwg01@yahoo.com.cn
Xue
Hui-bin
HB
Su
Chang-qing
CQ
Cui
Zhen-fu
ZF
Nie
Ming-ming
MM
Sham
Jonathan
J
Wu
Meng-chao
MC
Qian
Qi-jun
QJ
D000256:Adenoviridae / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000235:genetics; D043168:Angiostatins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014162:Transfection
D017500:Adenovirus E1A Proteins; D043168:Angiostatins