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.
Conclusion: 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.