Development of DC-based vaccine therapy by utilizing exosomes collected from healthy volunteer-derived DCs

利用从健康志愿者衍生的 DC 中收集的外泌体开发基于 DC 的疫苗疗法

• 批准号: 18591440
• 负责人: MORISAKI Takashi
• 金额: $ 2.39万
• 依托单位: Kyushu 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-18591440/
• 关键词: Dendritic cells; Exosomes; Vaccine; Standard; Cancer therapy; Molecule transplantation

Aim of this study is to develop a method for preparing dendritic cells (DCs), which have homogeneous ability of antigen presentation between individuals, as therapeutic tool for cancer patients. It is a unique point that exosomes secreted by DCs generated from healthy volunteers' peripheral blood mononuclear cells (PBMCs) are utilized for this ourpose.Data obtained during the research period are as follows:1) Methodology for qualitative and quantitative evaluation of DC-derived exosomes:We developed a new methodology for purification and qualitative and quantitative evaluation of exosomes by combination of ultracentrifugation, sucrose density, and BDLA-DR-bound beads. As a result, it was shown tat critical antigen presentation-related molecules, including MHC class II, CD80, CD86, and ICAM-1, are expressed highly and homogeneously on exosomes derived from healthy volunteer's DCs. On the other hand, expressions of these molecules were weak on exosomes derived from patient-derived DCs.In conclusion, it was strongly indicated that expression of HLA-DR on purified exosomes is a marker for qualitative and quantitative evaluation of DC-derived exosomes.2)Effects of DC"derived exosomes on differentiation and function of DCs:2-1: Survival prolongation of CD4+ T cells by exosomes collected from healty volunteer-derived DCs.2-2: Improved differentiation of patient-derived DCs by exosomes collected from healty volunteerderived DCs.2-3 increased NK cell activity by exosomes collected from healty volunteerderived DCs.2-4: Induction of cytotoxic T cells (CTLs) by exosomes collected from tumor cell-pulsed DCs.2-5: Survival prolongation of regulatory T cells by exosomes collectede from malignant effusions.3)Others:An interesting possibility that exosomes secreted from CE4-transfected DCs express CEA was indicated.

本研究的目的是开发一种制备树突状细胞（DC）的方法，树突状细胞在个体之间具有同质的抗原呈递能力，作为癌症患者的治疗工具。其独特之处在于，我们利用健康志愿者的外周血单核细胞（PBMC）产生的DC分泌的外泌体。研究期间获得的数据如下：1）DC来源的外泌体的定性和定量评估方法学：我们开发了一种结合外泌体纯化和定性和定量评估的新方法。 超速离心、蔗糖密度和 BDLA-DR 结合珠。结果表明，关键的抗原呈递相关分子，包括 MHC II 类、CD80、CD86 和 ICAM-1，在源自健康志愿者 DC 的外泌体上高度且均匀地表达。另一方面，这些分子在源自患者来源的DC的外泌体上表达较弱。总之，强烈表明纯化的外泌体上HLA-DR的表达是定性和定量评估DC来源的外泌体的标志物。2)DC来源的外泌体对DC的分化和功能的影响：2-1：CD4+T细胞的存活延长 从健康志愿者衍生的 DC 收集的外泌体。2-2：从健康志愿者衍生的 DC 收集的外泌体改善了患者衍生 DC 的分化。2-3 从健康志愿者衍生 DC 收集的外泌体增加了 NK 细胞活性。2-4：从脉冲肿瘤细胞收集的外泌体诱导细胞毒性 T 细胞 (CTL) DCs.2-5：从恶性渗出液中收集的外泌体延长了调节性T细胞的存活。3）其他：表明了CE4转染的DC分泌的外泌体表达CEA的有趣可能性。

项目成果

担癌間者胸腹水中の制御性T細胞(Treg細胞)増加の機序解析

癌症患者胸腹水中调节性T细胞（Treg细胞）增加的机制分析

• 发表时间: 2007
• 作者: 和田 純治;ほか
• 通讯作者: ほか

癌患者末梢血中の制御性T細胞(Treg細胞)増加の機序解析と癌免疫療法におけるTreg細胞測定の臨床的意義

癌症患者外周血调节性T细胞（Treg细胞）增加的机制分析及Treg细胞测量在癌症免疫治疗中的临床意义

• 发表时间: 2007
• 作者: 和田 純治;ほか
• 通讯作者: ほか

Activated Src and Ras induce gefitinib resistance by activation of signaling pathways downstream of epidermal growth factor receptor in human gallbladder adenocarcinoma cells

• DOI: 10.1007/s00280-006-0219-4
• 发表时间: 2006-11-01
• 期刊: CANCER CHEMOTHERAPY AND PHARMACOLOGY
• 影响因子: 3
• 作者: Qin, Baoli;Ariyama, Hiroshi;Nakano, Shuji
• 通讯作者: Nakano, Shuji

Regulatory T cells are possible effect prediction markers of immunother apy for cancer patients

调节性T细胞可能是癌症患者免疫治疗效果预测标志物

• 期刊: Anticancer Research (in press)
• 作者: Wada J;et. al.
• 通讯作者: et. al.

Regulatory T cells are possible effect prediction markers of immunotherapy for cancer patients

调节性T细胞可能是癌症患者免疫治疗效果预测标志物

• 期刊: Anticancer Research (in press)
• 作者: Wada;J;Yamasaki;A;Morisaki;T;Nagai;S;Yanai;K;Fuchino;K;Akiyoshi;T;Koga;K;Nakashima;H;Nakamura;M;Tanaka;M;Katano;M
• 通讯作者: M