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Development of the next generation cancer therapy using "Exosomes" by molecular tumor engineering technique

通过分子肿瘤工程技术开发使用“外泌体”的下一代癌症疗法

基本信息

批准号：
17390351
负责人：
KATANO Mitsuo
金额：
$ 9.79万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390351/
关键词：
Exosomes Small vesicles Dendritic cells Vaccine therapy Immunotherapy Cancerous ascites Regulatory T cells Functional molecules 細胞小胞免役療法悪性腫瘍癌性腹膜炎

项目摘要

Along a study plan, we report here results of research during the study period. 1. Making of high exosome-secretion cells : Monocyte-derived dendritic cells (DCs) secrete a large amount of exosomes and their secretion is stable. 2. Separation and purification of Exosomes : DCs-derived exosomes and tumor-derived exosomes were efficiently purified by anti-HLA DR antibodies and by the antibodies against tumor antigens, respectively. 3. Change to functional vesicles of exosomes : We introduced EGFR or CEA gene using adenovirus vectors to DCs. These DCs secreted exosomes expressing EGFR or CEA, respectively. In other words, the possibility that could produce arbitrary protein on exosome by gene transfection was shown. 4. Molecular biologic analysis of exosomes : It was confirmed that tumor-derived exosomes secrete various kinds of protein which are useful for cancer vaccine. Thus, a utility of tumor-derived exosomes as nanoparticle for supplying carcinoma-related molecules was confirmed. 5. Immunological functional analysis of exosomes : DCs-derived exosomes : 1) augmentation of natural killer cells activity, 2) functional improvement of cancer patients-derived DCs, and 3) survival prolongation of regulatory T cells. Cancer cell-derived exosomes : Induction of CTL-like cells. As described above, we clarified several unique biological and immunological characteristics of exosomes and suggested a clinical application of exosomes to tumor immunotherapy. On the other hand, it was a plan to express Patched on exosomes at first, but did not succeed. However, during this study period, we succeeded in making several anti-Patched antibodies that have neutralization activity.

按照研究计划，我们在此报告研究期间的研究结果。1.高外切体分泌细胞的制备：单核细胞来源的树突状细胞(DC)分泌大量外切体，且分泌稳定。2.外切体的分离和纯化：DC来源的外切体和肿瘤来源的外切体分别被抗HLADR抗体和抗肿瘤抗原抗体有效地纯化。3.外切体功能囊泡的改变：用腺病毒载体将EGFR或CEA基因导入DC。这些DC分别分泌表达EGFR和CEA的外切体。也就是说，通过基因转染法可以在外切体上产生任意蛋白质。4.外切体的分子生物学分析：证实肿瘤来源的外切体分泌多种可用于肿瘤疫苗的蛋白质。因此，证实了肿瘤来源的外切体作为供应肿瘤相关分子的纳米颗粒的用途。5.外切体的免疫功能分析：DC来源的外切体：1)增强自然杀伤细胞活性，2)改善癌症患者来源的DC的功能，3)延长调节性T细胞的存活时间。癌细胞衍生的外切体：CTL样细胞的诱导。如上所述，我们阐明了外切体的几个独特的生物学和免疫学特性，并建议将外切体应用于肿瘤免疫治疗。另一方面，最初是一个计划来表达exosome上的补丁，但没有成功。然而，在本研究期间，我们成功地制备了几种具有中和活性的抗补丁抗体。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

腫瘍制御学分野における「免疫学を基盤とした腫瘍制御法開発」の現状

肿瘤控制科学领域“基于免疫学的肿瘤控制方法的发展”现状

DOI：
发表时间：
2006
期刊：
福岡医学雑誌 97
影响因子：
0
作者：
Nakashima H;Nakamura M;Yamaguchi H;Yamanaka N;Akiyoshi T;Koga K;Tsuneyoshi M;Tanaka M;Katano M;片野光男
通讯作者：
片野光男

Paclitaxel probably enhances cytotoxicity of natural killer cells against breast carcinoma cells by increasing perforin production

DOI：
10.1007/s00262-004-0617-6
发表时间：
2005-05-01
期刊：
CANCER IMMUNOLOGY IMMUNOTHERAPY
影响因子：
5.8
作者：
Kubo, M;Morisaki, T;Katano, M
通讯作者：
Katano, M

Combination therapy of tumor cell-pulsed dendritic cells and activated lymphocytes for patients with disseminated carcinomas.

肿瘤细胞脉冲树突状细胞和活化淋巴细胞联合治疗播散性癌患者。

DOI：
发表时间：
2005
期刊：
Anticancer Reserarch 25
影响因子：
0
作者：
Nakashima H;Nakamura M;Yamaguchi H;Yamanaka N;Akiyoshi T;Koga K;Tsuneyoshi M;Tanaka M;Katano M;片野光男;Nakashima H. et al.;Tanaka T. et al.;Shibata S. et al.;Kubo M.et al.;Onishi H. et al.;Katano M. et al.
通讯作者：
Katano M. et al.

Nuclear Factor-KB Contributes to Hedgehog Signaling Pathway Activation through Sonic Hedgehog Induction in Pancreatic Cancer

核因子-KB 通过 Sonic Hedgehog 诱导胰腺癌中的 Hedgehog 信号通路激活