摘要
AIM:To test the efficacy of gene therapy in rat liver tumor, METHODS:A retroviral vector GCIL12EIL2PN encoding human IL-2(hIL-2)and mouse IL-12(mIL-12)fused gene and its packaging cell were constructed.The packaging cell lines contained of IL-2 and/or IL-12 genes were injected intrasplenically to transfect splenocyte at different time. The therapeutic effect,immune function and toxic effect were evaluated. RESULTS:The average survival times of the 4 groups using IL genes at days 1,3,5 and 7 after tumor implantation were 53.3±3.7,493±4.2,31.0±2.1 and 24.3±1.4 d respectively in IL-2/IL-12 fused gene group,25.0±2.5,23.5±2.0, 18.3±2.4 and 12.0±1.8 d respectively in IL-2 gene treatment group,and 39.0±4.8,32.0±3.9,23.0±2.5 and 19.4±2.1 d respectively in IL-12 gene treatment group(P<0.01,n=10). In the IL-12/IL-2 fused gene treatment group,30% of rats treated at days 1 and 3 survived more than 60 d and serum mIL-12 and hIL-2 levels were still high at day 3 after treatment.Compared with IL alone,NK cell activity was strongly stimulated by IL-2/IL-12 gene.Microscopy showed that livers were infiltrated by a number of lymphocytes. CONCLUSION:IL-2 and/or IL-12 genes injected directly into spleen increase serum IL-2 and IL-12 levels and enhance the NK cell activity,which may inhibit the liver tumor growth.The therapy of fused gene IL-2/IL-12 is of low toxicity and relatively high NK cell activity.Our data suggest that IL-2/IL-12 fused gene may be a safe and efficient gene therapy for liver tumor.The gene therapy should be administrated as early as possible.
METHODS: A retroviral vector GCIL12EIL2PN encoding human IL-2 (hIL-2) and mouse IL-12 (raiL-12) fused gene and its packaging cell were constructed. The packaging cell lines contained of IL-2 and/or IL-12 genes were injected intrasplenically to transfect splenocyte at different time.The therapeutic effect, immune function and toxic effect were evaluated.RESULTS: The average survival times of the 4 groups using IL genes at days 1, 3, 5 and 7 after tumor implantation were 53.3±3.7, 49.3±4.2, 31.0±2.1 and 24.3±1.4 d respectively in IL-2/IL-12 fused gene group, 25.0±2.5, 23.5±2.0,18.3±2.4 and 12.0±1.8 d respectively in IL-2 gene treatment group, and 39.0+4.8, 32.0+3.9, 23.0+2.5 and 19.4+2.1 d respectively in IL-12 gene treatment group (P<0.01, n=-10).In the IL-12/IL-2 fused gene treatment group, 30% of rats treated at days 1 and 3 survived more than 60 d and serum raiL-12 and hIL-2 levels were still high at day 3 after treatment. Compared with IL alone, NK cell activity was strongly stimulated by IL-2/IL-12 gene. Microscopy showed that livers were infiltrated by a number of lymphocytes.CONCLUSION: IL-2 and/or IL-12 genes injected directly into spleen increase serum IL-2 and IL-12 levels and enhance the NK cell activity, which may inhibit the liver tumor growth. The therapy of fused gene IL-2/IL-12 is of low toxicity and relatively high NK cell activity. Our data suggest that IL-2/IL-12 fused gene may be a safe and efficient gene therapy for liver tumor. The gene therapy should be administrated as early as possible.
基金
Supported by the National Natural Science Foundation of China,No.30271476 and No.39970838 and the Shanghai Science and technology Key Problem Foundation,No.034119837
