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Development of new cancer immunotherapy using activation of Toll like receptor against gastrointestinal cancer

利用Toll样受体激活对抗胃肠道癌症开发新的癌症免疫疗法

基本信息

批准号：
18591479
负责人：
MATSUDA Kenji
金额：
$ 2.14万
依托单位：
Wakayama Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591479/
关键词：
CDG-ODN peptide immunotherapy

项目摘要

CpG oligodeoxynucleotides (CpG-ODNs) mimic bacterial DNA and induce immune response that comprise innate immunity and acquired Th-1 biased cellular immunity. Recently, 3 types of CpG-ODNs (CpG-A, CpG-B and CpG-C) have been identified based on distinct immunologic activities on human plasmacytoid dendritic cells (PDCs) and B cells. We investigated the activity of these three types of CpG-ODN to enhance the induction of peptide specific CTLs. First, human PBMCs of healthy volunteers were stimulated with each types of CpG-ODN for 48 hours. Samples of the culture media were analyzed for cytokine induction with ELISA method. CpG-A and CpG-C, but not CpG-B, were potent inducers of IFN-α. Second, Flu peptide-specific CTLs were generated from PBMCs cultured with Flu peptide and each types of CpG-ODN for 2 weeks to compare the lytic activity against A24-LCL cells pulsed with Flu peptide in a standard Cr lysis assay. Flu peptide-specific cytotoxicity was enhanced in the presence of each type of CpG-ODN and especially CpG-A and CpG-C showed higher lytic activity than CpG-B. This CpG ODN-induced enhancement of cytotoxicity was disappeared when PDCs were depleted from PBMCs. In conclusion, our results showed that CpG-A and CpG-C might be the superior vaccine adjuvant to CpG-B at least in vitro.

CpG寡脱氧核苷酸（CpG-ODNs）模拟细菌DNA并诱导包括天然免疫和获得性Th-1偏向的细胞免疫的免疫应答。近年来，基于对人浆细胞样树突状细胞（PDCs）和B细胞的不同免疫活性，已鉴定出3种CpG-ODN（CpG-A、CpG-B和CpG-C）。我们研究了这三种类型的CpG-ODN增强肽特异性CTL诱导的活性。首先，用每种类型的CpG-ODN刺激健康志愿者的人PBMC 48小时。用ELISA方法分析培养基样品的细胞因子诱导。CpG-A和CpG-C是IFN-α的强诱导剂，而CpG-B不是。其次，从用Flu肽和每种类型的CpG-ODN培养2周的PBMC产生Flu肽特异性CTL，以在标准Cr裂解测定中比较针对用Flu肽脉冲的A24-LCL细胞的裂解活性。各CpG-ODN均能增强流感病毒抗原特异性的细胞毒活性，CpG-A和CpG-C的细胞毒活性明显高于CpG-B。这种CpG ODN诱导的细胞毒性增强在PDCs从PBMC中耗尽时消失。总之，我们的结果表明，CpG-A和CpG-C可能是上级疫苗佐剂，至少在体外比CpG-B。