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Combined Interleukin 12 and Interleukin 2 Gene Therapy for Hepatocellular Carcinoma in A Rat Model
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Abstract:
Objective:To determine the feasibility and efficacy of combined murine interleukin 12 (mIL-12) and human interleukin 2 (hIL-2) gene therapy for hepatocellular carcinoma in a rat model. Methods: The retroviral vector encoding mIL-12/hIL-2 gene was constructed and then transfected into packaging cell line. The cells were injected into rats in the established hepatoma at different time points. The therapeutic effect, immune function and toxicological response were evaluated. Results:Intratumoral injection of recombinant retroviral vector encoding mIL-12/hIL-2 gene resulted in marked hepatoma regression. The 35 d survival rates of the subgroups treated on the first，third，fifth and seventh day after tumor implantation were 100%, 100%, 30% and 10% respectively. The average survival time of the IL-12+IL-2 treatment group was superior to those of the physiological saline group（P＜0.01), retroviral empty vector group（P＜0.01), IL-2 treatment group(P＜0.01) and IL-12 treatment group（P＜0.01). The immunological study showed that the number of hepatoma infiltrating lymphocytes was increased in the IL-12+IL-2 treatment group. Conclusion:The retroviral packaging cell line encoding mIL-12 and hIL-2 gene via intratumoral injection inhibits the growth of hepatocellular carcinoma significantly. The therapeutical effects of early administration is superior to that of later one.
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