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:
  • 金额:
    $ 9.79万
  • 依托单位:
  • 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

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:
  • 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:
  • 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:
  • 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
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nakashima H.;et al.
  • 通讯作者:
    et al.
Modification of glucocorticoid sensitivity by MAP kinase signaling pathways in glucocorticoid-induced T-cell apoptosis
  • DOI:
    10.1016/j.exphem.2006.06.018
  • 发表时间:
    2006-11-01
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Tanaka, Tomoko;Okabe, Taijiro;Nawata, Hajime
  • 通讯作者:
    Nawata, Hajime
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KATANO Mitsuo其他文献

KATANO Mitsuo的其他文献

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{{ truncateString('KATANO Mitsuo', 18)}}的其他基金

Development of cancer therapy targeting Hedgehog signaling network
针对 Hedgehog 信号网络的癌症疗法的开发
  • 批准号:
    24390303
  • 财政年份:
    2012
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Estabishment of G0 cancer cell model for the development of therapeutic strategy to target seceding from and re-entry into cell cycle in cancer cell
建立G0癌细胞模型,用于制定针对癌细胞脱离和重新进入细胞周期的治疗策略
  • 批准号:
    23659616
  • 财政年份:
    2011
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Functional analysis of Gli1 molecule for developing a new inclusive therapy against many tumor species
Gli1 分子的功能分析,用于开发针对多种肿瘤的新的包容性疗法
  • 批准号:
    21390363
  • 财政年份:
    2009
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Comprehensive analysis of morphogenesis signaling pathways for the development of organ-specific anticancer therapy
形态发生信号通路综合分析,用于器官特异性抗癌治疗的开发
  • 批准号:
    19390337
  • 财政年份:
    2007
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of a tumor cell bank for next generation immunotherapy
开发下一代免疫疗法的肿瘤细胞库
  • 批准号:
    15390380
  • 财政年份:
    2003
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
A higher immune system model by combination of several types of artificial tissues (connective tissue, carcinoma tissue, and lymphoid tissue)
多种人工组织(结缔组织、癌组织、淋巴组织)组合而成的高级免疫系统模型
  • 批准号:
    13470240
  • 财政年份:
    2001
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
New therapy combined with immunology, molecular biology and medical technology for patients with peritoneal carcinosis
免疫学、分子生物学和医疗技术相结合的腹膜癌新疗法
  • 批准号:
    12557106
  • 财政年份:
    2000
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
New strategy for cancerous peritonitis : cyclosporin-A combination therapy
癌性腹膜炎新策略:环孢素A联合治疗
  • 批准号:
    11671253
  • 财政年份:
    1999
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The prognosic value of the transcription of tumor growth-related genes in endoscopic biopsy specimens from patients with malignancies of digestive tracts
消化道恶性肿瘤内镜活检标本中肿瘤生长相关基因转录的预后价值
  • 批准号:
    08671460
  • 财政年份:
    1996
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Multicytokine-producintg mononuclear cell therapy for cancer patients
针对癌症患者的产生多细胞因子的单核细胞疗法
  • 批准号:
    04670788
  • 财政年份:
    1992
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

Molecular mechanism of cancer derived small vesicles related tumor malignancies
癌源性小囊泡相关肿瘤的分子机制
  • 批准号:
    17K15005
  • 财政年份:
    2017
  • 资助金额:
    $ 9.79万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
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