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

• 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

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-ODN) 模仿细菌 DNA 并诱导免疫反应，包括先天免疫和获得性 Th-1 偏向细胞免疫。最近，已开发出 3 种类型的 CpG-ODN（CpG-A、CpG-B 和 CpG-C）。基于对人浆细胞样树突状细胞 (PDC) 和 B 细胞的不同免疫活性，我们研究了这三种类型的 CpG-ODN 增强的活性。首先，用每种类型的 CpG-ODN 刺激健康志愿者的人 PBMC 48 小时，并使用 ELISA 方法分析培养基样品的细胞因子诱导。其次，Flu 肽特异性 CTL 是由与 Flu 肽和每种类型的 PBMC 一起培养的。 CpG-ODN 2 周，以比较在标准 Cr 裂解测定中用 Flu 肽脉冲的 A24-LCL 细胞的裂解活性，每种类型的 CpG-ODN，尤其是 CpG-A 和 CpG-ODN 的存在增强了 Flu 肽特异性细胞毒性。当 PBMC 中的 PDC 被耗尽时，CpG-C 表现出比 CpG-B 更高的裂解活性。总之，我们的结果表明，至少在体外，CpG-A 和 CpG-C 可能是优于 CpG-B 的疫苗佐剂。

项目成果

Streptococcal preparation OK-432 promotes the capacity of dendritic cells(DCs) to prime carcinoembryonic antigen(CEA)-specific T lymphocyte responses induced with genetically modified DCs that express CEA

链球菌制剂 OK-432 促进树突状细胞 (DC) 启动表达 CEA 的转基因 DC 诱导的癌胚抗原 (CEA) 特异性 T 淋巴细胞反应的能力

• 发表时间: 2008
• 期刊: Int J Oncol 32(2)
• 作者: Ojima T;et. al.
• 通讯作者: et. al.

Successful cancer vaccine therapy for carcinoembryonic antigen(CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice

使用表达 CEA 和 T 辅助型 1 细胞因子的转基因树突状细胞在 CEA 转基因小鼠中成功治疗表达癌胚抗原 (CEA) 的结肠癌

• 发表时间: 2007
• 期刊: Int J Cancer 120(3)
• 作者: Ojima T;et. al.
• 通讯作者: et. al.

Difference between CpG-A, CpG-B and CpG-C about the adjuvant effect to enhance human peptide-specific CTL induction in vitro

CpG-A、CpG-B和CpG-C在体外增强人肽特异性CTL诱导的佐剂作用的差异

• 发表时间: 2007
• 作者: Katsuda M;et. al.
• 通讯作者: et. al.

Repeat reduction surgery after an initial hepatectomy for patients with colotectal cancer

结肠直肠癌患者初次肝切除术后重复减容手术

• 发表时间: 2007
• 期刊: Oncology Reports 18
• 作者: Matsuda K;et. al.
• 通讯作者: et. al.

Successful cancer vaccine therapy for carcinoembryonnic antigen(CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice

使用表达 CEA 和 T 辅助细胞 1 型细胞因子的转基因树突状细胞在 CEA 转基因小鼠中成功治疗表达癌胚抗原 (CEA) 的结肠癌

• 发表时间: 2007
• 期刊: Int J Cancer 120(3)
• 作者: Ojima T;et. al.
• 通讯作者: et. al.