[Combined gene therapy for murine liver cancer with interleukin-18 and cytosine deaminase genes].

OBJECTIVE

To investigate the synergistic antitumor effects of murine IL-18 and CD/5FC gene therapy on mice bearing liver cancer.

METHODS

A retrovirus vector pGCEN/IL-18 containing murine interleukin-18 gene was constructed. The retrovirus carrying IL-18 gene was used to infect murine liver cancer cell MM45T.Li, and proved to secret biological active IL-18. In mice bearing liver cancer, (60)Co-irradiated MM45T.Li/IL-18 vaccine was inoculated subcutaneously once a week for two weeks, and/or AdCD was injected intratumorally with 5FC injected i.p. for 8 days.

RESULTS

Thirty days from the treatment, the tumor volume of control group was 1580 approximately 1625 mm(3), MM45T.Li/IL-18 vaccine group was 366 +/- 159 mm(3), AdCD/5FC group was 438 +/- 65 mm(3), and combined IL-18 and AdCD/ 5FC therapy group was 15 +/- 7 mm(3) (P<0.05). The tumor volume in single gene therapy group reduced to the smallest after three-week treatment, but grew large again, while the tumor volume in combined therapy group still remained small. The median survival time in control group was 50.0 approximately 51.5 days, MM45T.Li/IL-18 group was 65 days, AdCD/5FC group was 57 days versus 75 days for combined gene therapy group (P<0.05), and with more abundant infiltration of CD4+ and CD8+ lymphocytes around the tumor in combined gene therapy group.

CONCLUSIONS

Combined gene therapy with IL-18 and CD/5FC can reduce the tumor volume and elicit the antitumor immunity of the host, which is superior to the single gene therapy for murine liver cancer.