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Translational Research on the Use of Genetically Modified HumanNatural Killer Cells for Refractory Leukemia.

Research Project

Project/Area Number 21591349
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionNiigata University

Principal Investigator

IMAI Chihaya  新潟大学, 医歯学総合病院, 講師 (90419284)

Co-Investigator(Renkei-kenkyūsha) IMAMURA Masaru  新潟大学, 医歯学総合病院, 特任助教 (80464006)
SAKIKO Yoshida  新潟大学, 医歯学総合病院, 特任助教 (30535183)
TAKACHI Takayuki  新潟大学, 医歯学総合病院, 医員 (70444164)
Project Period (FY) 2009 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsNK細胞 / chimeric receptor / 細胞療法 / 難治性白血病 / 臍帯血移植 / CD19 / 4-1BB / CD28 / キメラ型受容体 / B細胞性腫瘍 / CD4^+ T細胞 / CD4^+T細胞
Research Abstract

Genetic modification and ex vivo expansion of human natural killer cells were investigated in order to overcome cellular resistance of leukemia, with special interests in the following subjects: 1) feasibility and applicability of the method using the peripheral blood (PB) obtained from patients who suffer from relapse after cord blood transplantation (CBT), 2) improvement of the signal transduction of the anti-CD19 chimeric antigen receptors, 3) improvement of NK cell persistence after in vivo infusion. In this study, ex vivo expansion and genetic modification of donor-derived NK cells from the patients’ PB was shown to be feasible in CBT recipients. The donor-derived NK cells from the patients’ PB were able to expand ex vivo, were susceptible to retroviral gene transduction and exerted powerfulcytotoxicity against CD19^+ leukemia cells via anti-CD19-chimeric receptors.

Report

(5 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (47 results)

All 2013 2012 2011 2010 2009

All Journal Article (25 results) (of which Peer Reviewed: 23 results) Presentation (17 results) (of which Invited: 2 results) Book (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [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
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Alveolar rhabdomyosarcoma after treatment of osteosarcoma2013

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

      Pediatrics International

      Volume: 未定

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immune- deficiency2012

    • Author(s)
      Kawai T, Imai C et al
    • Journal Title

      Blood

      Volume: 119 Issue: 23 Pages: 5458-66

    • DOI

      10.1182/blood-2011-05-354167

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 家系に複数の脾臓摘出者を認め遺伝性球状赤血球症と考えられていたHb Koeln症の一例2012

    • Author(s)
      笠原 靖史、細貝 亮介、高地 貴行、吉田 咲子、今村 勝、今井 千速.
    • Journal Title

      日本小児血液・がん学会雑誌

      Volume: 49 Pages: 138-141

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disseminated BCG Infection Mimicking Metastatic Nasopharyngeal Carcinoma in anImmunodeficient Child with a Novel Hypomorphic NEMO Mutation2011

    • Author(s)
      Imamura M, Takachi T, Yoshida S, Imai C
    • Journal Title

      J Clin Immunol

      Volume: 31 Issue: 5 Pages: 802-10

    • DOI

      10.1007/s10875-011-9568-9

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphoblastic lymphoma with mature B-cell immunophenotype and MLL-AF9 in a child2011

    • Author(s)
      Takachi T, Iwabuchi H, Imamura M, Imai C
    • Journal Title

      Pediatr Blood Cancer

      Volume: 57 Issue: 7 Pages: 1251-1252

    • DOI

      10.1002/pbc.23228

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 小児・思春期白血病に対する本邦共通プロトコールの策定2011

    • Author(s)
      今井千速
    • Journal Title

      新潟医学会雑誌

      Volume: 125 Pages: 69-74

    • Related Report
      2011 Annual Research Report
  • [Journal Article] 急性リンパ性白血病治療中に発症し、アムホテリシンBリポソーム製剤が奏効した接合菌症の疑われる脳膿瘍の1例2011

    • Author(s)
      細貝亮介、今井千速, ほか
    • Journal Title

      日本小児血液学会雑誌

      Volume: 25 Pages: 97-101

    • NAID

      10029312185

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autonomously functioning thyroid nodule in a four-year-old boy with Sotos syndrome2011

    • Author(s)
      Nyuzuki H, Nagasaki K, Matsuyama H, Tomita M, Imai C, et al
    • Journal Title

      Pediatr Int

      Volume: 53(1) Pages: 137-138

    • NAID

      10029557486

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma2010

    • Author(s)
      Mihara K, Imai C, et al
    • Journal Title

      Br J Haematol

      Volume: 151 Issue: 1 Pages: 37-46

    • DOI

      10.1111/j.1365-2141.2010.08297.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reactive tonsillar enlargement with strong 18F-FDG uptake after chemotherapy for tonsillar diffuse large B cell lymphoma2010

    • Author(s)
      Hosokai R, Imai C, et al
    • Journal Title

      J Pediatr Hematol Oncol

      Volume: 33 Issue: 2 Pages: e87-e88

    • DOI

      10.1097/mph.0b013e3181f69205

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NK細胞療法の基礎と展望(総説)2010

    • Author(s)
      今井千速
    • Journal Title

      小児がん

      Volume: 47 Pages: 268-274

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma2010

    • Author(s)
      Mihara K, Yanagihara K, Takigahira M, Kitanaka A, Imai C, et al
    • Journal Title

      Br J Haematol

      Volume: 151(1) Pages: 37-46

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure2009

    • Author(s)
      Nemoto T, Imai C, et al
    • Journal Title

      Pediatr Hematol Oncol

      Volume: 26 Pages: 520-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activated T-cell-mediated immune therapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma2009

    • Author(s)
      Mihara K, Imai C, et al
    • Journal Title

      J Immunother

      Volume: 32 Issue: 7 Pages: 737-43

    • DOI

      10.1097/cji.0b013e3181adaff1

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy2009

    • Author(s)
      Fujisaki H, Imai C, et al
    • Journal Title

      Cancer Res

      Volume: 69 Issue: 9 Pages: 4010-7

    • DOI

      10.1158/0008-5472.can-08-3712

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Replicative potential of human natural killer cells2009

    • Author(s)
      Fujisaki H, Kakuda H, Imai C, et al
    • Journal Title

      Br J Haematol

      Volume: 145 Issue: 5 Pages: 606-13

    • DOI

      10.1111/j.1365-2141.2009.07667.x

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel homozygous8-base pair deletion mutation in the glycoprotein Ibalpha gene in a patient with Bernard-Soulier syndrome2009

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

      Blood Coagul Fibrinolysis

      Volume: 20 Issue: 6 Pages: 470-4

    • DOI

      10.1097/mbc.0b013e32832b27fa

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] NK細胞療法の基礎と展望~NK細胞の体外増幅と遺伝子改変を中心に2009

    • Author(s)
      今井千速
    • Journal Title

      第51回日本小児血液学会・第25回日本小児がん学会教育セッションテキスト

      Pages: 110-114

    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Journal Article] Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy.2009

    • Author(s)
      Fujisaki H, Imai C, et al.
    • Journal Title

      Cancer Research 69(9)

      Pages: 4010-4017

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel homozygous 8-base pair deletion mutation in the glycoprotein Ibα gene in a patient with Bernard-Soulier syndrome2009

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

      Blood Coagulation & Fibrinolysis 20(6)

      Pages: 470-474

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replicative potential of human natural killer cells.2009

    • Author(s)
      Fujisaki H, Imai C, et al.
    • Journal Title

      British Journal of Haematology 145(5)

      Pages: 606-613

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activated T-cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell non-Hodgkin lymphoma.2009

    • Author(s)
      Mihara K, Imai C, et al.
    • Journal Title

      Journal of Immunotherapy 32

      Pages: 737-743

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure2009

    • Author(s)
      Nemoto T, Imai C, et al.
    • Journal Title

      Pediatric Hematology and Oncology 26(7)

      Pages: 520-525

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A 2-year-old boy with a stage III yold sac tumor occurring in an intra-abdominal retained testis.2009

    • Author(s)
      Hirayama Y, Imai C, et al.
    • Journal Title

      Journal of Pediatric Surgery 44(12)

      Pages: 2395-2398

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Ex Vivo Expansion and Genetic Modification of Human Natural Killer Cells -An approach for treating refractory leukemia and cancer. In Symposium 5: Cellular Therapy2012

    • Author(s)
      Imai C
    • Organizer
      The 54th Annual Meeting of the Japanese Society of Pediatric Hematology and Oncology
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2012-12-01
    • Related Report
      2012 Final Research Report
  • [Presentation] アロNK細胞輸注療法に向けて~ヒトNK細胞の体外増幅と遺伝子改変法の開発2012

    • Author(s)
      今井千速
    • Organizer
      第34回日本造血細胞移植学会総会ワークショップ「免疫細胞療法の基礎」
    • Place of Presentation
      大阪市
    • Year and Date
      2012-02-24
    • Related Report
      2012 Final Research Report
  • [Presentation] アロNK細胞輸注療法に向けて~ヒトNK細胞の体外増幅と遺伝子改変法の開発(ワークショップ;座長からの招請)2012

    • Author(s)
      今井千速
    • Organizer
      第34回日本造血細胞移植学会総会
    • Place of Presentation
      大阪国際会議場(大阪府)(招待講演)
    • Year and Date
      2012-02-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ex Vivo Expansion and Genetic Modification of Human Natural Killer Cells –An approach for treating refractory leukemia and cancer2012

    • Author(s)
      Chihaya Imai
    • Organizer
      The 54th Annual Meeting of the Japanese Society of Pediatric Hematology and Oncology, In Symposium 5: Cellular Therapy (International symposium)
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 白血病治療とNK細胞2012

    • Author(s)
      今井千速
    • Organizer
      平成24年度JACLS/CCLSG合同夏季セミナー
    • Place of Presentation
      福島県耶麻郡北塩原村
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Peripheral Blood as a Possible Source of Donor-Derived NK Cells for Ex Vivo Expansion and Genetic Modification for Post-Transplant Cellular Immunotherapy In Cord Blood Recipients2010

    • Author(s)
      Imai C
    • Organizer
      The 52th American Society of Hematology annual meeting
    • Place of Presentation
      Orlando, FL
    • Year and Date
      2010-12-04
    • Related Report
      2012 Final Research Report
  • [Presentation] Peripheral Blood as a Possible Source of Donor-Derived NK Cells for Ex Vivo Expansion and Genetic Modification for Post-Transplant Cellular Immunotherapy In Cord Blood Recipients.2010

    • Author(s)
      Imai C.
    • Organizer
      The 52th American Society of Hematology annualmeeting(poster presentation)
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2010-12-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] NK 細胞の体外増幅と遺伝子改変:難治性腫瘍に対する細胞療法に向けて2010

    • Author(s)
      今井千速
    • Organizer
      Meet the Professor in NAGOYA
    • Place of Presentation
      名古屋市
    • Year and Date
      2010-10-15
    • Related Report
      2012 Final Research Report
  • [Presentation] NK細胞の体外増幅と遺伝子改変:難治性腫瘍に対する細胞療法に向けて2010

    • Author(s)
      今井千速
    • Organizer
      Meet the Professor in NAGOYA
    • Place of Presentation
      名古屋市(招待講演)
    • Year and Date
      2010-10-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 小児・思春期白血病に対する本邦共通プロトコールの策定2010

    • Author(s)
      今井千速
    • Organizer
      第658回新潟医学会シンポジウム「血液疾患の治療をめぐる進歩」
    • Place of Presentation
      新潟市
    • Year and Date
      2010-05-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Myeloablative auto-transplant followed by KIRL-MM RI-CBT for a 10y.o. Boy with NMYC-amp stage IV neuroblastoma.2010

    • Author(s)
      Imai C.
    • Organizer
      Japan-Korea Neuroblastoma Symposirm
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] 造血幹細胞移植とNK細胞2010

    • Author(s)
      今井千速
    • Organizer
      第16回新潟同種造血幹細胞移植研究会
    • Place of Presentation
      新潟市
    • Year and Date
      2010-02-05
    • Related Report
      2012 Final Research Report
  • [Presentation] 造血幹細胞移植とNK細胞(特別講演).2010

    • Author(s)
      今井千速
    • Organizer
      第16回新潟同種造血幹細胞移植研究会
    • Place of Presentation
      新潟県新潟市
    • Year and Date
      2010-02-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] NK細胞療法の基礎と展望~NK細胞の体外増幅と遺伝子改変(教育講演)2009

    • Author(s)
      今井千速
    • Organizer
      第25回日本小児がん学会,がん教育セッション
    • Place of Presentation
      千葉
    • Year and Date
      2009-11-28
    • Related Report
      2012 Final Research Report
  • [Presentation] NA細胞療法の基礎と展望~NK細胞の体外増幅と遺伝子改変(教育講演)2009

    • Author(s)
      今井千速
    • Organizer
      第25回日本小児がん学会(がん教育セッション)
    • Place of Presentation
      千葉県浦安市
    • Year and Date
      2009-11-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 臍帯血移植生着後の患者血液からのドナー由来Natural Killer(NK)細胞の体外増幅2009

    • Author(s)
      今井千速
    • Organizer
      第71回日本血液学会
    • Place of Presentation
      京都市
    • Year and Date
      2009-10-23
    • Related Report
      2012 Final Research Report
  • [Presentation] 臍帯血移植生着後の患者血液からのドナー由来Natural Killer(NK)細胞の体外増幅2009

    • Author(s)
      今井千速
    • Organizer
      第71回日本血液学会
    • Place of Presentation
      京都府京都市
    • Year and Date
      2009-10-23
    • Related Report
      2009 Annual Research Report
  • [Book] 小児の鉄欠乏性貧血.今目の治療指針2011(山口徹, 北原光夫, 福井次矢総編集)2011

    • Author(s)
      今井千速(分担執筆)
    • Publisher
      医学書院
    • Related Report
      2010 Annual Research Report
  • [Book] 遺伝性球状赤血球症.G6PD欠乏症(グルコース6リン酸脱水素酵素欠乏症).家庭医学大全科2010

    • Author(s)
      今井千速(分担執筆)
    • Publisher
      法研
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] Chimeric receptors with 4-1BB stimulatory signaling domain2013

    • Inventor(s)
      Dario Campana and Chihaya Imai
    • Industrial Property Rights Holder
      Dario Campana ,Chihaya Imai, and St. Jude Children's Research Hospital
    • Acquisition Date
      2013-03-19
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Chimeric receptors with 4-1BB stimulatory signaling domain (US Patent)2012

    • Inventor(s)
      Campana D and Imai C
    • Industrial Property Rights Holder
      Campana D and Imai C
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-07-12
    • Acquisition Date
      2013-03-19
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] Expansion of NK cells and therapeutic uses thereof2011

    • Inventor(s)
      Dario Campana and Chihaya Imai
    • Industrial Property Rights Holder
      Dario Campana ,Chihaya Imai, and St. Jude Children's Research Hospital
    • Acquisition Date
      2011-09-27
    • Related Report
      2012 Final Research Report

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Published: 2009-04-01   Modified: 2019-07-29  

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