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Reconstitution of human tumor microenvironment in second generation humanized NOG mice - Development of evaluation systems for cancer immunotherapy

Research Project

Project/Area Number 16K18404
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

Hanazawa Asami  公益財団法人実験動物中央研究所, 実験動物研究部, 研究員 (40633334)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords腫瘍モデル動物 / ヒト化マウス / 次世代NOGマウス / 腫瘍微小環境 / TAM / MDSC / IL-6 Tgマウス / M-CSF Tgマウス / ヒト腫瘍モデル動物 / 疾患モデル / 腫瘍 / 免疫学
Outline of Final Research Achievements

TAMs (Tumor-associated macrophages) are one of the immunosuppressive myeloid cells which are induced in cancer patients. Although these cells are considered as a key of cancer immune therapy, animal models which allow the evaluation of medicinal effect against these human immunosuppressive cells have not been established. In this study, we induced human TAMs in the animal models based on NOG hIL-6 Tg mice which promote the differentiation of human monocytes and macrophages. Moreover, we indicated that the character and the function of the TAMs in this mice are relating for the cells in cancer patients. In addition, we established the new 2nd generation NOG mice including NOG hM-CSF Tg mice which are usefully for the establishment of human cancer animal models have been established.

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は近年目覚ましく発展しているが、その評価に適した実験動物は未だ確立されていない。本研究において樹立されたNOG hIL-6 Tgマウスをはじめとする新規ヒト腫瘍モデル動物は、TAM等のがん患者に特有な細胞を含む様々なヒト免疫細胞を体内に保持し、がん細胞と免疫細胞の相互作用を再現しており、がん免疫療法における新規治療法や新規薬剤の免疫機構への影響を評価することができる。よって、本研究はがん免疫療法の発展に大きく貢献するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] Generation of Human Immunosuppressive Myeloid Cell Populations in Human Interleukin-6 Transgenic NOG Mice2018

    • Author(s)
      Hanazawa Asami、Ito Ryoji、Katano Ikumi、Kawai Kenji、Goto Motohito、Suemizu Hiroshi、Kawakami Yutaka、Ito Mamoru、Takahashi Takeshi
    • Journal Title

      Front Immunol.

      Volume: 9 Pages: 1-16

    • DOI

      10.3389/fimmu.2018.00152

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] NOG-human M-CSF transgenic mice enhance differentiation and maturation of human monocytes and macrophages2017

    • Author(s)
      Asami Hanazawa
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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