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Development of in vivo cytotoxicity assay system using humanized mice increasing human natural killer cells

Research Project

Project/Area Number 25871075
Research Category

Grant-in-Aid for Young Scientists (B)

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

Principal Investigator

Katano Ikumi  公益財団法人実験動物中央研究所, その他部局等, 研究員 (90442558)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsヒト化マウス / NK細胞 / ヒト免疫 / hIL-2 / hIL-15 / hIL-2
Outline of Final Research Achievements

We previously reported that human NK cells are predominately developed in NOG-hIL-2 Tg mice after human hematopoietic stem cell (HSC) transplantation. In this study, we assessed in vivo antibody-dependent-cellular-cytotoxicity (ADCC) activity using human HSC-transferred NOG-hIL-2 Tg mice engrafted with CCR4 expressing Hodgkin’s lymphoma cell line L428. After treatment with an anti-CCR4 antibody, tumor growth was slightly suppressed in NOG-hIL-2 Tg mice. To improve the function of NK cells, we generated a NOG-hIL-15 Tg mouse. Although human mature NK cells were dominantly differentiated in NOG-hIL-15 Tg mice, they immediately died within 8 weeks after HSC transplantation. In contrast, human peripheral blood-derived mature NK cells succeeded to be maintained over 3 months after transplantation without death. Moreover, these NK cells showed in vivo cytotoxic activity against engrafted K562 cells. Therefore, NOG-hIL-15 Tg mice are useful tools for investigation of in vivo NK cytotoxicity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Predominant Development of Mature and Functional Human NK Cells in a Novel Human IL-2-Producing Transgenic NOG Mouse2015

    • Author(s)
      Katano, I. Takahashi, T. Ito, R. Kamisako, T. Mizusawa, T. Ka, Y. Ogura, T. Suemizu, H. Kawakami, Y. Ito, M.
    • Journal Title

      J Immunol

      Volume: 194 Issue: 7 Pages: 3513-3525

    • DOI

      10.4049/jimmunol.1401323

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Visualization of the human CD4(+) T-cell response in humanized HLA-DR4-expressing NOD/Shi-scid/gammac(null) (NOG) mice by retrogenic expression of the human TCR gene2015

    • Author(s)
      Takahashi, T. Katano, I. Ito, R. Ito, M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 456 Issue: 1 Pages: 219-224

    • DOI

      10.1016/j.bbrc.2014.11.062

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] NOD-Rag2null IL-2Rγnull mice: an alternative to NOG mice for generation of humanized mice.2014

    • Author(s)
      Katano I, Ito R, Kamisako T, Eto T, Ogura T, Kawai K, Suemizu H, Takahashi T, Kawakami Y, Ito M.
    • Journal Title

      Exp Anim

      Volume: 63 Pages: 321-330

    • NAID

      130004677826

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel enhanced green fluorescent protein-expressing NOG mouse for analyzing the microenvironment of xenograft tissues.2014

    • Author(s)
      Higuchi Y, Kawai K, Yamamoto M, Kuronuma M, Ando Y, Katano I, Nakamura M, Suemizu H.
    • Journal Title

      Exp Anim

      Volume: 63 Pages: 55-62

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Establishment of a Human Allergy Model Using Human IL-3/GM-CSF-Transgenic NOG Mice.2013

    • Author(s)
      Ito, R., T. Takahashi, I. Katano, K. Kawai, T. Kamisako, T. Ogura, M. Ida-Tanaka, H. Suemizu, S. Nunomura, C. Ra, A. Mori, S. Aiso, and M. Ito.
    • Journal Title

      J Immunol

      Volume: 191 Issue: 6 Pages: 2890-2899

    • DOI

      10.4049/jimmunol.1203543

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Human interleukin-15 transgenic NOG mice support the long-term maintenance of human mature NK cells from peripheral blood2016

    • Author(s)
      Ikumi Katano, Takeshi Takahashi, Ryoji Ito, Asami Hanazawa, Mamoru Ito
    • Organizer
      5th International Workshop on Humanized Mice (IWHM5)
    • Place of Presentation
      Switzerland, University of Zurich
    • Year and Date
      2016-01-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Human interleukin-15 transgenic NOG mice support the long-term maintenance of human mature NK cells from peripheral blood2015

    • Author(s)
      Ikumi Katano, Takeshi Takahashi, Ryoji Ito, Asami Hanazawa, Yutaka Kawakami, Mamoru Ito
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌、札幌コンベンションセンター
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒトIL-15遺伝子導入NOGマウスはヒト末梢血由来成熟NK細胞を長期間維持できる2015

    • Author(s)
      片野いくみ、高橋武司、伊藤亮治、花澤麻美、高橋利一、末水洋志、河上裕、伊藤守
    • Organizer
      第62回日本実験動物学会総会
    • Place of Presentation
      京都テルサ
    • Year and Date
      2015-05-28 – 2015-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒトIL-15遺伝子導入NOGマウスはヒト末梢血由来成熟NK細胞を長期間維持できる2015

    • Author(s)
      片野いくみ、高橋武司、伊藤亮治、花澤麻美、高橋利一、末水洋志 、河上裕、伊藤守
    • Organizer
      第62回日本実験動物学会総会
    • Place of Presentation
      京都、京都テルサ
    • Year and Date
      2015-05-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] Characterization of human Eosinophil in HSC-transferred NOG-human IL-5 transgenic mice2013

    • Author(s)
      Ikumi Katano, Takeshi Takahashi, Ryoji Ito, Mamoru Ito
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      千葉・幕張メッセ
    • Related Report
      2013 Research-status Report
  • [Presentation] Predominant Development of Mature and Functional Human NK Cells in a Novel Human IL-2 Producing Transgenic NOD-scid,IL-2Rg KO (NOG) Mouse2013

    • Author(s)
      Ikumi Katano, Takeshi Takahashi, Ryoji Ito, Mamoru Ito
    • Organizer
      The 4th International Workshop on Humanized Mice (IWHM4)
    • Place of Presentation
      韓国・ソウル
    • Related Report
      2013 Research-status Report
  • [Presentation] Functional NK cells developed from human hematopoietic stem cell in human interleukin-2 transgenic NOG mice2013

    • Author(s)
      Ikumi Katano, Ryoji Ito, Takeshi Takahashi, Mamoru Ito
    • Organizer
      15th International Congress of Immunology
    • Place of Presentation
      イタリア・ミラノ(Mico)
    • Related Report
      2013 Research-status Report
  • [Patent(Industrial Property Rights)] ヒトIL-15分泌免疫不全マウス2015

    • Inventor(s)
      伊藤守、片野いくみ
    • Industrial Property Rights Holder
      伊藤守、片野いくみ
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-107932
    • Filing Date
      2015-05-27
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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