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Studies towards development of more effective NK cell therapy: Finding genetic determinants for selection of best NK cell donors and a novel method for transfer of chimeric antigen receptor protein

Research Project

Project/Area Number 25461581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNiigata University

Principal Investigator

Imai Chihaya  新潟大学, 医歯学系, 准教授 (90419284)

Co-Investigator(Renkei-kenkyūsha) SAKIKO YOSHIDA  新潟大学, 医歯学総合研究科, 客員研究員 (30535183)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsNK細胞 / 白血病 / がん / KIR / NKG2D / trogocytosis / 造血幹細胞移植 / リンパ腫 / CD19 / Trogocytosis / NK cell / chimeric receptor / KIR haplotype
Outline of Final Research Achievements

In this study towards development of more effective natural killer (NK) cell therapy against cancer and leukemia, we investigated on the genetic determinants that can predict individuals’ NK cell functions. In healthy adults, we observed significant association of NKG2D haplotypes with NK cell functions. We also observed association of KIR haplotypes with in-vitro cytokine/chemokine production. In addition, we found that donor KIR haplotypes significantly affected the clinical outcomes such as acute GVHD after allogeneic hematopoietic stem cell transplantations. In addition to the abovementioned studies, we investigated on a novel method to transfer chimeric antigen receptor into human primary NK cells by using trogocytosis phenomenon to confer them capability to kill malignant cells in an antigen-specific manner. Expression by using trogocytosis was possible, but expression levels were not enough for clinical translation and will require further modification and improvement.

Report

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

    (14 results)

All 2016 2015 2014 2013

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia2016

    • Author(s)
      Nakazawa Y, Matsuda K, Kurata T, Sueki A, Tanaka M, Sakashita K, Imai C, Wilson MH, Koike K
    • Journal Title

      J Hematol Oncol

      Volume: 9 Issue: 1 Pages: 27-27

    • DOI

      10.1186/s13045-016-0256-3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Secondary osteosarcoma arising from osteochondroma following autologous stem cell transplantation with total-body irradiation for neuroblastoma: A case report.2015

    • Author(s)
      Kawashima H, Ogose A, Hotta T, Imai C, Imamura M, Endo N.
    • Journal Title

      Oncol Lett

      Volume: 10(2) Pages: 1026-1030

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-152014

    • Author(s)
      Imamura M, Shook D, Kamiya T, Shimasaki N, Chai SM, Coustan-Smith E, Imai C, Campana D
    • Journal Title

      Blood

      Volume: 124 Issue: 7 Pages: 1081-1088

    • DOI

      10.1182/blood-2014-02-556837

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] 4-1BB Chimeric Antigen Receptors2014

    • Author(s)
      Campana D, Schwarz H, Imai C
    • Journal Title

      Cancer J

      Volume: 20 Issue: 2 Pages: 134-140

    • DOI

      10.1097/ppo.0000000000000028

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing2014

    • Author(s)
      Kudo K, Imai C, Lorenzini P, Kamiya T, Kono K, Davidoff AM, Chng WJ, Campana D
    • Journal Title

      Cancer Res

      Volume: 74 Issue: 1 Pages: 93-103

    • DOI

      10.1158/0008-5472.can-13-1365

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ヒトNK細胞の体外増幅と遺伝子改変 ~難治性白血病・がんの征圧に向けて2013

    • Author(s)
      今井千速
    • Journal Title

      日本小児血液・がん学会雑誌

      Volume: 50 Pages: 341-349

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 微小残存病変を用いた急性リンパ性白血病治療戦略2013

    • Author(s)
      今井千速
    • Journal Title

      小児内科

      Volume: 45 Pages: 1134-1136

    • Related Report
      2013 Research-status Report
  • [Journal Article] Alveolar rhabdomyosarcoma after treatment of osteosarcoma.2013

    • Author(s)
      Kasahara Y, Iwabuchi H, Takachi T, Hosokai R, Yoshida S, Imamura M, Watanabe A, Umezu H, Hotta T, Ogose A, Imai C
    • Journal Title

      Pediatr Int.

      Volume: 55 Issue: 4 Pages: 527-530

    • DOI

      10.1111/ped.12070

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autoimmunity and persistent RAS- mutated clones long after the spontaneous regression of JMML2013

    • Author(s)
      Takagi M, Imai C, et al
    • Journal Title

      Leukemia

      Volume: 27 Issue: 9 Pages: 1926-1928

    • DOI

      10.1038/leu.2013.82

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Donor KIR haplotype B exacerbates acute GVHD in HLA-mismatched hematopoietic cell transplantation: A single-center retrospective analysis2016

    • Author(s)
      Ryosuke Hosokai, Masayoshi Masuko, Yasuhiko Shibazaki, Akihiko Saitoh, Tatsuo Furukawa, and Chihaya Imai
    • Organizer
      European Hematology Association, 21st Congress
    • Place of Presentation
      デンマーク・コペンハーゲン
    • Year and Date
      2016-06-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] キメラ型抗原受容体(CAR):初期開発の経験から2016

    • Author(s)
      今井千速
    • Organizer
      東京都小児がん診療連携協議会・TCCSG(東京小児がん研究グループ)共同開催症例検討会
    • Place of Presentation
      聖路加国際病院トイスラーホール(東京都中央区)
    • Year and Date
      2016-02-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 小児がん・白血病の最近の話題 ~整形外科的問題を呈する症例を中心に~2014

    • Author(s)
      今井千速
    • Organizer
      第2回Niigata OS Meeting
    • Place of Presentation
      新潟グランドホテル、新潟市中央区
    • Year and Date
      2014-10-22
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] ドナーKIRハプロタイプBはATG不使用同種造血幹細胞移植において重症急性GVHDの危険因子となる可能性がある2014

    • Author(s)
      細貝亮介、今井千速、柴崎康彦、増子正義、古川達雄
    • Organizer
      第36回日本造血細胞移植学会
    • Place of Presentation
      沖縄県宜野湾市
    • Related Report
      2013 Research-status Report
  • [Presentation] 抗CD19キメラ型受容体とNK細胞体外増幅法の開発2013

    • Author(s)
      今井千速
    • Organizer
      第26回東北BMT研究会
    • Place of Presentation
      宮城県仙台市
    • Related Report
      2013 Research-status Report
    • Invited

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

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