Combination of IL-12 and IL-18 of electro-gene therapy synergistically inhibits tumor growth.
Combination of IL-12 and IL-18 of electro-gene therapy synergistically inhibits tumor growth.
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DOI：
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发表时间：
2003-03
影响因子：
2
通讯作者：
T. Tamura;T. Nishi;T. Goto;H. Takeshima;Y. Ushio;T. Sakata
中科院分区：
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作者：
T. Tamura;T. Nishi;T. Goto;H. Takeshima;Y. Ushio;T. Sakata
背景我们先前的研究表明，IL-12电基因治疗(EGT)可诱导显著的抗肿瘤免疫。然而，由于IL-18与IL-12协同作用增强Th1反应和干扰素-γ，我们设计了一种使用IL-12+IL-18的EGT方案，目的是增强单独使用IL-12获得的抗肿瘤效果。材料与方法将携带IL-12或IL-18基因的表达载体共转染小鼠CT26皮下肿瘤。半定量RT-PCR分析治疗后肿瘤中干扰素-γ的表达和CD8+T细胞的存在。结果IL-12+IL-18 EGT对肿瘤生长的抑制作用明显强于IL-12 EGT，这与瘤内较高水平的干扰素-γ相一致。IL-12和IL-12+IL-18 EGT均证实CD8+T细胞对肿瘤组织的侵袭增强。最后，IL-12+IL-18 EGT，而不是IL-12 EGT，显著抑制未经治疗的对侧肿瘤。结论EGT联合IL-12、IL-18可能是一种有效的抗肿瘤基因治疗方法。
BACKGROUND We previously showed that IL-12 electro-gene therapy (EGT) induces significant antitumor immunity. However, because interleukin (IL)-18 acts synergistically with IL-12 to augment Th1 responses and interferon (IFN)-gamma, we designed an EGT protocol using IL-12 + IL-18 with the aim of enhancing the antitumor effects obtained with IL-12 alone. MATERIALS AND METHODS Expression plasmids harboring the gene for IL-12 or IL-18 were cotransferred to subcutaneous murine CT26 tumors. Subsequent expression of IFN-gamma and the presence of CD8+ T cells within treated tumors were analyzed by semiquantitative RT-PCR. RESULTS IL-12 + IL-18 EGT inhibited tumor growth significantly better than IL-12 EGT, which was consistent with significantly higher intratumoral levels of IFN-gamma. Enhanced infiltration of tumor tissues by CD8+ T cells was confirmed with both IL-12 and IL-12 + IL-18 EGT. Finally, IL-12 + IL-18 EGT, but not IL-12 EGT, significantly suppressed untreated contralateral tumors. CONCLUSION EGT with IL-12 and IL-18 is potentially an effective antitumor gene therapy.