Development of novel immuno-gene therapy for gastrointestinal cancer using antigen presenting function of heat shock protein

利用热休克蛋白的抗原呈递功能开发新型胃肠癌免疫基因疗法

基本信息

批准号：
10671132
负责人：
KITAGAWA Yuko
金额：
$ 2.05万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671132/
关键词：
heat shock protein gastrointestinal cancer immuno-gene therapy tumor rejection antigen presentation dendritic cell

项目摘要

The anti-tumor effect of heat-shock proteins (hsp) derived from CMS7-ME tumor was investigated. CMS7-ME, cell line was established by a HER2/neu transduction into the CMS7 derived from BALB/c mice fibrosarcoma. Three kinds of hsps, gp-96, hsp-70, hsp-90 were extracted from CMS7-ME and subcutaneously inoculated into the other mice. CMS7-ME tumor was implanted into these hsp-immunized mice. In gp96 or hsp-70 treated group, growth inhibitory effect implanted of CMS7-ME was observed. There is no anti-tumor effect in hsp-90 treated group.In the model of CT-26, N-nitroso-N-methylurethane induced BALB/c colonic tumor, an anti-tumor effect of CT-26 derived hsps was investigated, gp-96 derived from CT-26 showed growth inhibitory effect to CT-26 tumor. There is no growth inhibitory effect of CT-26 derived hsp-70 or hsp-90 treated groups. The complex of gp96 extracted from normal liver and CT-26 specific peptide, AH-1 showed anti-tumor effect in this model. However an induction of AH-1 specific cytotoxic T cells was not detected in this experiment.Anti-tumor effect of dendritic cells (DC) pulsed with gp96 derived from CT-26 was compared with that of DC pulsed with AH-1. DC pulsed with gp96 derived from CT-26 showed more significant growth inhibitory effect to CT-26 tumor in comparison with AH-1 pulsed DC.These results suggest that the role of tumor derived hsp in the antigen presenting process.Further investigation would be required to confirm the mechanisms of these effects as a pre-clinical investigation.

研究了源自 CMS7-ME 肿瘤的热休克蛋白 (hsp) 的抗肿瘤作用。 CMS7-ME 细胞系通过 HER2/neu 转导至源自 BALB/c 小鼠纤维肉瘤的 CMS7 中而建立。从CMS7-ME中提取gp-96、hsp-70、hsp-90三种热休克蛋白，并皮下接种到其他小鼠体内。 CMS7-ME 肿瘤被植入这些 hsp 免疫小鼠体内。在gp96或hsp-70处理组中，观察到植入的CMS7-ME的生长抑制作用。 hsp-90治疗组没有抗肿瘤作用。在CT-26、N-亚硝基-N-甲基氨基甲酸酯诱导的BALB/c结肠肿瘤模型中，研究了CT-26衍生的hsps的抗肿瘤作用，源自CT-26的gp-96对CT-26肿瘤显示出生长抑制作用。 CT-26衍生的hsp-70或hsp-90治疗组没有生长抑制作用。从正常肝脏中提取的gp96与CT-26特异性肽AH-1的复合物在此模型中显示出抗肿瘤作用。然而，在该实验中没有检测到AH-1特异性细胞毒性T细胞的诱导。将用源自CT-26的gp96脉冲的树突状细胞(DC)的抗肿瘤作用与用AH-1脉冲的DC进行比较。与AH-1脉冲的DC相比，用CT-26衍生的gp96脉冲的DC对CT-26肿瘤表现出更显着的生长抑制作用。这些结果表明肿瘤衍生的hsp在抗原呈递过程中的作用。需要进一步研究作为临床前研究来确认这些作用的机制。