Published online Aug 1, 2004. doi: 10.3748/wjg.v10.i15.2190
Revised: February 20, 2004
Accepted: February 21, 2004
Published online: August 1, 2004
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, 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 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.