[Antitumor effect of gene therapy with recombinant adenovirus-mediated human interleukin-2 gene transfer and its mechanism].
OBJECTIVE
To explore the transfection, expression, antitumor effect and mechanism of a replication-deficient adenovirus vector expressing human IL-2 gene (advhIL-2) in a murine H22 hepatocellular carcinoma model.


METHODS
KM mice bearing tumor 100-200 mm3 were injected intratumorally with advhIL-2, adv-LacZ or with PBS alone. The tumor evolution was recorded every 3 days. The transfection and expression of the recombinant adenovirus were examined with X-gal staining and RT-PCR respectively. The splenic LAK and CTL activities were assayed with 51Cr 4 hours release. The infiltration of CD4+ and CD8+ T cells in the tumors were analyzed with immunofluorescence.


RESULTS
It was found that the recombinant adenovirus can bring about in vivo effective transfection and expression. The continuosly expressive time of advhIL-2 is longer than 12 days. AdvhIL-2 has dose-dependent anti-tumor effect. The mice received a dose of 2 x 10(9) pfu advhIL-2 divided into halves for two injections developed tumor more slowly and survived much longer than the mice treated with PBS (P < 0.01). Moreover, advhIL-2 increased the splenic LAK and CTL activities, CD4+ and CD8+ T cell infiltration in the H22 tumors significantly.


CONCLUSIONS
Adenovirus-mediated hIL-2 gene treatment has significant antitumor activity in pre-established hepatocellular carcinoma in mice. Antitumor immunity might be responsible for the therapeutic effect.
Du
Junrong
J
Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Ran
Yinwei
Y
Lin
Zhirong
Z
Zheng
Changwen
C
Wei
Haiyan
H
Wang
Xiujie
X
Zhou
Liang
L
Ren
Yi
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy; D007376:Interleukin-2 / Q000235:genetics* / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009368:Neoplasm Transplantation; D011897:Random Allocation; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D007376:Interleukin-2