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

IL-4抗胃肠道癌的基础和治疗方法

基本信息

批准号：
06671291
负责人：
KATANO Mithuo
金额：
$ 1.28万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671291/
关键词：
Interleukin-4(IL-4)gastric carcinoma IL-4 receptor Gene transfection

项目摘要

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.

本研究在体外研究IL-4对胃癌和结肠癌细胞株生长抑制作用的基础上，对IL-4作为抗胃肠道肿瘤药物进行了临床前评价。体内研究未能证明IL-4（每只小鼠高达200 μ g）对移植到裸鼠体内的胃癌细胞生长的抑制作用。然而，由于低剂量IL-4联合TNF-α或IFN-γ在体外有效地抑制癌细胞的生长，因此需要测试体内细胞因子组合研究。虽然多次将IL-4基因转染进胃癌细胞，但我们用ELISA法检测不到这些细胞释放IL-4。另外的研究表明，IL-4在基因转染的黑素瘤细胞系M101中可检测到，范围为2，500 pg/106个细胞/24小时，并且在转染后2周检测不到。这些结果表明所测试的癌细胞之间的IL-4产生的差异活性。而IL-4基因转染的黑色素瘤细胞表达Class-1、Class-2和ICAM-1较对照组高，提示IL-4基因转染的细胞可作为肿瘤疫苗。IL-4基因转染胃肠道癌细胞的研究有待继续和建立。近年来，树突状细胞已被证明是最有效的抗原呈递细胞，并且IL-4和GM-CSF已被证明对于这些细胞的诱导和增殖是最重要的。我们计划用IL-4作为肿瘤抗原提呈树突状细胞的体内刺激因子用于免疫治疗。