Basic and therapeutic approaches of interleukin-4 against gastro-intestinal tract cancers

在前人体外研究证实人白细胞介素-4对胃癌和结肠癌细胞系生长抑制作用的基础上，本研究旨在对白细胞介素-4作为人胃肠道肿瘤的抗癌药物进行临床前评价。体内研究未能证明IL-4（每只小鼠高达200 ug）对裸鼠移植胃癌细胞的生长有抑制作用。然而，由于低剂量IL-4联合tnf - α或ifn - γ在体外能有效抑制癌细胞的生长，体内细胞因子联合研究还需进一步验证。虽然多次将IL-4基因转染到胃癌细胞中，但ELISA法无法检测到胃癌细胞中IL-4的释放。进一步的研究表明，IL-4在基因转染的黑色素瘤细胞系M101中检测到，范围为2,500 pg/106个细胞/24小时，转染后2周无法检测到。这些结果表明不同癌细胞之间IL-4产生活性的差异。然而，IL-4转染的黑色素瘤细胞比对照组表达更多的Class-1、2和icam -1，提示IL-4基因转染的细胞可以作为肿瘤疫苗。IL-4基因转染胃肠道癌细胞的研究需要继续和建立。最近树突状细胞已被证明是最有效的抗原呈递细胞，IL-4和GM-CSF已被证明对这些细胞的诱导和增殖最重要。我们计划使用IL-4作为肿瘤抗原呈递树突状细胞的体内刺激剂进行免疫治疗。

Based on the previous in vitro study which demonstrated the growth inhibitory effect of human interleukin-4 on the gastric and colonic carcinoma cell lines, in this stuby, we aimd the preclinical evaluation of IL-4 as anti-cancer agents against human gastro-intestinal tract cancers. In vivo study failed in demonstrating the inhibition of IL-4(up to 200 ug for each mouse)on the growth of gastric carcinoma cells transplanted into nude mice. However, because low dose IL-4 combined with TNF-alpha or IFN-gamma effectively inhibited the growth of the carcinoma cells in vitro, in vivo cytokine combination study needs to be tested. Although IL-4 gene transfection into gastric carcinoma cells was repeatedly carried out, we could not detect IL-4 release from those cells by ELISA assay. Additional study showed that IL-4 was detectable in the gene transfected melanoma cell line M101 ranged from 2,500 pg/106 cells/24 hr, and was undetectable 2 weeks after the transfection. These results indicated the differential activity of IL-4 production between carcinoma cells tested. However, the IL-4 transfected melanoma cells expressed more Class-1 and 2, andICAM-1 than the control, suggesting that the IL-4 gene transfected cells can be tumor vaccines. IL-4 gene transfection study using gastro-intestinal tract carcinoma cells needs to be continued and established. Recently dendritic cells have been demonstrated to be the most potent antigen-presenting cells and IL-4 and GM-CSF have been shown to be the most important for induction and proliferation of those cells. We are plannning to use IL-4 as invivo stimulator of tumor antigen presenting dendritic cells for immunotherapy.