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Analysis of anti-bladder tumor with BCB derivative producing fusion protein between Ag85B and IL-2 or IL-18

BCB衍生物产生Ag85B与IL-2或IL-18融合蛋白的抗膀胱肿瘤分析

基本信息

批准号：
20590458
负责人：
KATO Michio
金额：
$ 3万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590458/
关键词：
膀胱癌治療 BCG IL-2 IL-18 結核抗原粘膜アジュバント LT 下痢毒素LT 融合蛋白質下痢毒素 LT

项目摘要

Two immunological methods such as LAK(IL-2LAK) and TIL are used for the treatment of cancer. In LAK, NK and T cells, especially, cytotoxic T lymphocyte (CTL), are activated by autocrine or paracrine pathway through IL-2/IL-2R and kill cancer cells. In this experiment, we already reported that when mice were intra-nasally immunized with inactivated BCG plus mutant LT, the cellular immunity for inactivated BCG was highly induced (Vaccine,24,3591,2006). Moreover, when the spleen cells from mice intra-nasally immunized with inactivated BCG plus mLT or live BCG were prepared and stimulated by inactivated or live BCG, respectively,in vitro, IL-2 was induced higher in the spleen cells from mice immunized with inactivated BCG plus mLT than those with live BCG. These data suggest the possibility that when mice immunized with inactivated BCG plus mLT might induce identical anti-cancer affect as live BCG. Then, we examined whether the immunization of mice with inactivated BCG plus mLT or some cytokine such as IL-2 or IL-18 might induce similar anti-cancer effect, especially for bladder cancer, to live BCG. Moreover, we construct the vector containing Ag85B-IL-2 or Ag85B-IL-2IL-18 fusion gene to determine whether BCG carrying these constructed vector might decrease the growth of bladder tumor.

两种免疫学方法如LAK（IL-2LAK）和TIL用于治疗癌症。在LAK中，NK细胞和T细胞，特别是细胞毒性T淋巴细胞（CTL）通过IL-2/IL-2 R的自分泌或旁分泌途径被激活并杀伤癌细胞。在该实验中，我们已经报道了当用灭活BCG加突变LT鼻内免疫小鼠时，高度诱导了对灭活BCG的细胞免疫（Vaccine，24，3591，2006）。此外，当制备灭活BCG + mLT或活BCG鼻内免疫小鼠的脾细胞并分别用灭活或活BCG刺激时，灭活BCG + mLT免疫小鼠的脾细胞中IL-2的诱导高于活BCG免疫小鼠。这些数据表明，当用灭活BCG + mLT免疫小鼠时，可能诱导与活BCG相同的抗癌作用。然后，我们研究了用灭活BCG + mLT或某些细胞因子如IL-2或IL-18免疫小鼠是否可以诱导类似于活BCG的抗癌效果，特别是对膀胱癌。此外，我们还构建了含Ag 85 B-IL-2或Ag 85 B-IL-2 IL-18融合基因的载体，以确定携带这些构建的载体的BCG是否具有抑制膀胱肿瘤生长的作用。