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Generation of TRAIL positive NK cells from hematopoietic stem cells / iPS cells in vitro for anti-HCC immunotherapy

Research Project

Project/Area Number 24591880
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionHiroshima University

Principal Investigator

TANAKA Yuka  広島大学, 医歯薬保健学研究院(医), 准教授 (90432666)

Co-Investigator(Kenkyū-buntansha) OHDAN Hideki  広島大学, 医歯薬保健学研究院(医), 教授 (10363061)
ISHIYAMA Kohei  広島大学, 大学病院, 病院助教 (50437589)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsNK細胞 / 肝臓癌 / 細胞免疫療法
Outline of Final Research Achievements

We have previously reported that IL-2-stimulated CD56+ cells derived from the liver exert vigorous cytotoxicity against HCC. To differentiate NK cells, we incubated bone marrow-derived CD34+ hematopoietic progenitor cells in 5% serum-supplemented X-VIVO-15 medium containing SCF, Flt-3, IL-7, and IL-15. These NK cells expressed NKp46, a specific receptor of NK cells, and were phenotypically similar to resident NK cells, i.e. they expressed TRAIL, NKG2D, and CD226. The propagated NK cells produced IFN-γ. The propagated NK cells exhibited vigorous cytotoxicity against HCC cell lines by using 51Cr release assay. We have also developed a method to differentiate CD34+ hematopoietic progenitor cells from fibroblast-derived iPS cells. The use of NK cells for immunotherapy relies on the availability of large numbers of purified NK cells with optimal anti-HCC activities. This adaptive immunotherapy with these cells may be a promising modality to prevent the recurrence of HCC after hepatectomy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (9 results)

All 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results)

  • [Journal Article] Quantitative effect of natural killer cell licensing on hepatocellular carcinoma recurrence after curative hepatectomy.2014

    • Author(s)
      Tanimine N, Tanaka Y, Kobayashi T, Tashiro H, Miki D, Imamura M, Aikata H, Tanaka J, Chayama K, Ohdan H.
    • Journal Title

      Cancer Immunol Res.

      Volume: 2 Pages: 1142-1147

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fasting Enhances TRAIL-Mediated Liver Natural Killer Cell Activity via HSP70 Upregulation.2014

    • Author(s)
      Dang VT, Tanabe K, Tanaka Y, Tokumoto N, Misumi T, Saeki Y, Fujikuni N, Ohdan H.
    • Journal Title

      PLoS One.

      Volume: 9 Issue: 10 Pages: e110748-e110748

    • DOI

      10.1371/journal.pone.0110748

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of alloimmune T cell responses on hepatitis C virus replication in liver transplant recipients.2014

    • Author(s)
      Tanaka Y, Ohira M, Tashiro H, Imamura M, Chayama K, Ohdan H.
    • Journal Title

      Hum Immunol.

      Volume: 75 Issue: 12 Pages: 1259-1267

    • DOI

      10.1016/j.humimm.2014.09.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] リモデリングNK 細胞によるHCV 感染抑制および制癌効果2014

    • Author(s)
      田中友加, 清水誠一, 大段秀樹.
    • Organizer
      第50回日本移植学会総会
    • Place of Presentation
      東京
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Influence of adoptive immunotherapy employing allograft liver-resident lymphocytes on alloimmune responses2014

    • Author(s)
      Tanaka Y, Ohdan H
    • Organizer
      WTC2014
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2014-07-26 – 2014-07-31
    • Related Report
      2014 Annual Research Report
  • [Presentation] 肝移植後活性化NK 細胞移入療法がT 細胞抗ドナー応答に与える影響解析2014

    • Author(s)
      田中友加,石山宏平, 大平真裕, 清水誠一, 井手健太郎, 尾上隆司, 小林剛, 田代裕尊, 大段秀樹.
    • Organizer
      第32回日本肝移植研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-03 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Generation of NK cells from hematopoietic stem cells in vitro for anti-HCV and anti-HCC immunotherapy: Evaluation using human hepatocyte chimeric mice2014

    • Author(s)
      Shimizu S, Tanaka Y, Hotta R, Ohdan H.
    • Organizer
      ILTS 2014
    • Place of Presentation
      London, United Kingdom
    • Year and Date
      2014-06-04 – 2014-06-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Unlicensed NK Cells Differentiated from CD34+ Hematopoietic Progenitor Cells Exhibit Anti-HCC and Anti-HCV Activity2013

    • Author(s)
      Ryuichi Hotta, Yuka Tanaka, Seiichi Shimizu, Masahiro Ohira, Kohei Ishiyama, Nobuhiko Hiraga, Kazuaki Chayama, Hideki Ohdan
    • Organizer
      American Transplant Congress2013
    • Place of Presentation
      Seattle, America
    • Related Report
      2013 Research-status Report
  • [Presentation] Hotta R, Ishiyama K, Ohira M, Igarashi Y, Tanaka Y, Onoe T, Ide K, Tashiro H, Ohdan H. Adoptive Immunotherapy with Donor Derived-Liver Natural Killer Cells Prevents HCC Recurrence after Liver Transplantation in Recipients Exceeding the Milan Criteria.2012

    • Author(s)
      Hotta R, Ishiyama K, Ohira M, Igarashi Y, Tanaka Y, Onoe T, Ide K, Tashiro H, Ohdan H
    • Organizer
      American Transplantation Congress 2012
    • Place of Presentation
      Boston, America
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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