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Establishment of T lymphocytes expressing chimeric antigen receptor for leukemic stem cells

Research Project

Project/Area Number 24390260
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pediatrics
Research InstitutionShinshu University

Principal Investigator

KOIKE Kenichi  信州大学, 学術研究院医学系, 教授 (40143979)

Co-Investigator(Kenkyū-buntansha) SAKASHITA Kazuo  信州大学, 医学部附属病院, 特任研究員 (10345746)
NAKAZAWA Yozo  信州大学, 学術研究院医学系(医学部附属病院), 講師 (60397312)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords白血病性幹細胞 / キメラ抗原受容体T細胞 / 小児白血病 / 若年性骨髄単球性白血病 / CD34陽性細胞 / GM-CSF receptor / 免疫療法 / 骨髄異形成症候群 / CAR T細胞
Outline of Final Research Achievements

We evaluated anti-proliferative potential of T cells non-virally engineered to bind to granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR.CAR T cells) against juvenile myelomonocytic leukemia (JMML) CD34+ cells. The co-culture of healthy or JMML GMR.CAR T cells with CD34+ cells of JMML patients in the presence of stem cell factor (SCF), thrombopoietin (TPO) and interleukin-3 for 2 days significantly decreased the total colony growth. Seven-day co-culture of GMR.CAR T cells with JMML CD34+ cells resulted in a marked suppression on the expansion of CD34+ cells, particularly CD34+CD38- cells, under stimulation with SCF+TPO on AGM-S3 cells. Meanwhile, GMR.CAR T cells exerted no effects on the colony growth of normal CD34+ cells. Thus, our GMR.CAR T cells may provide a novel adoptive immunotherapy for this disease.

Report

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

    (30 results)

All 2015 2014 2013 2012

All Journal Article (15 results) (of which Peer Reviewed: 14 results,  Acknowledgement Compliant: 6 results) Presentation (8 results) Book (7 results)

  • [Journal Article] In vitro expansion of CD34+CD38- cells under stimulation with hematopoietic growth factors on AGM-S3 cells in juvenile myelomonocytic leukemia.2015

    • Author(s)
      Sakashita K, Kato I, Daifu T, Saida S, Hiramatsu H, Nishinaka Y, Ebihara Y, Ma F, Matsuda K, Saito S, Hirabayashi K, Kurata T, Uyen LT, Nakazawa Y, Tsuji K, Heike T, Nakahata T, Koike K.
    • Journal Title

      Leukemia

      Volume: in press

    • NAID

      120007110642

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Reduced-toxicity myeloablative conditioning consisting of 8-Gy total body irradiation, cyclophosphamide and fludarabine for pediatric hematological malignancies.2015

    • Author(s)
      Hirabayashi K, Nakazawa Y, Sakashita K, Kurata T, Saito S, Yoshikawa K, Tanaka M, Yanagisawa R, Koike K.
    • Journal Title

      Sci Rep

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.2014

    • Author(s)
      Saito S, Nakazawa Y, Sueki A, Matsuda K, Tanaka M, Yanagisawa R, Maeda Y, Sato Y, Okabe S, Inukai T, Sugita K, Wilson MH, Rooney CM, Koike K.
    • Journal Title

      Cytotherapy

      Volume: 16 Pages: 1257-69

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Myeloid progenitors with PTPN11 and non-RAS pathway gene mutations are refractory to treatment with 6-mercaptopurine in juvenile myelomonocytic leukemia.2014

    • Author(s)
      Matsuda K, Nakazawa Y, Iwashita C, Kurata T, Hirabayashi K, Saito S, Tanaka M, Yoshikawa K, Yanagisawa R, Sakashita K, Sasaki S, Honda T, Koike K.
    • Journal Title

      Leukemia

      Volume: 28 Pages: 1545-8

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.2014

    • Author(s)
      Al-Kzayer LF, Sakashita K, Al-Jadiry MF, Al-Hadad SA, Uyen LT, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Hasan JG, Al-Abdullah HM, Inoshita T, Kamata M, Sughayer MA, Madanat FF, Koike K.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 61 Pages: 1980-5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Analysis of Class I and II Aberrations in Iraqi Childhood Acute Myeloid Leukemia Using Filter Paper Cards.2014

    • Author(s)
      Al-Kzayer LF, Uyen LT, Al-Jadiry MF, Al-Hadad SA, Al-Badri SA, Ghali HH, Ameen NA, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Hasan JG, Al-Abdullah HM, Al-Ani MH, Saber PA, Khalil HM, Inoshita T, Kamata M, Koike K, Sakashita K.
    • Journal Title

      Ann Hematol

      Volume: 93 Pages: 949-55

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Analysis of Class I and II Aberrations in Iraqi Childhood Acute Myeloid Leukemia Using Filter Paper Cards.2014

    • Author(s)
      Al-Kzayer LF, Uyen LT, Al-Jadiry MF, Al-Hadad SA, Al-Badri SA, Ghali HH, Ameen NA, Liu T, Matsuda K, Abdulkadhim JM, Al-Shujairi TA, Matti ZI, Hasan JG, Al-Abdullah HM, Al-Ani MH, Saber PA, Khalil HM, Inoshita T, Kamata M, Koike K, Sakashita K.
    • Journal Title

      Annals of Hematology

      Volume: 2014 Jan 25

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Usefulness of allogeneic hematopoietic stem cell transplantation in first complete remission for pediatric blastic plasmacytoid dendritic cell neoplasm with skin involvement: a case report and review of literature.2013

    • Author(s)
      Sakashita K, Saito S, Yanagisawa R Miyuki Tanaka M, Yoshikawa K, Hirabayashi K, Tsukahara K, Motobayashi M, Nakazawa Y, Koike K.
    • Journal Title

      Pediatr Blood Cancer

      Volume: 60 Issue: 11 Pages: E140-E142

    • DOI

      10.1002/pbc.24622

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful cord blood transplantation after repeated transfusions of unmobilized neutrophils in addition to antifungal treatment in an infant with chronic granulomatous disease complicated by invasive pulmonary aspergillosis.2013

    • Author(s)
      Shigemura T, Nakazawa Y, Yoshikawa K, Hirabayashi K, Saito S, Kobayashi N, Sakashita K, Shiohara M, Wada T, Shimodaira S, Agematsu K and Koike K.
    • Journal Title

      Transfusion

      Volume: 54 Issue: 3 Pages: 516-21

    • DOI

      10.1111/trf.12325

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Replaced platelet concentrates containing a new additive solution, M-sol: safety and efficacy for pediatric patients.2012

    • Author(s)
      Yanagisawa R, Sakashita K
    • Journal Title

      Transfusion.

      Volume: 53 Issue: 9 Pages: 2053-60

    • DOI

      10.1111/trf.12025

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term haematological improvement after non-intensive or no chemotherapy in juvenile myelomonocytic leukaemia and poor correlation with adult myelodysplasia spliceosome-related mutations.2012

    • Author(s)
      Matsuda K, Sakashita K
    • Journal Title

      Br J Haematol.

      Volume: 157 Issue: 5 Pages: 647-50

    • DOI

      10.1111/j.1365-2141.2012.09063.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia2012

    • Author(s)
      Doisaki S, Muramatsu H, Shimada A, Takahashi Y, Mori-Ezaki M, Sato M, Kawaguchi H, Kinoshita A, Sotomatsu M, Hayashi Y, Furukawa-Hibi Y, Yamada K, Hoshino H, Kiyoi H, Yoshida N, Sakaguchi H, Narita A, Wang X, Ismael O, Xu Y, Nishio N, Tanaka M, Hama A, Koike K, Kojima S
    • Journal Title

      Blood

      Volume: 120 Issue: 7 Pages: 1485-1488

    • DOI

      10.1182/blood-2012-02-406090

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards2012

    • Author(s)
      Al-Kzayer LF, Sakashita K, Matsuda K, Al-Hadad SA, Al-Jadiry MF, Abed WM, Abdulkadhim JM, Al-Shujairi TA, Hasan JG, Al-Abdullah HM, Al-Ani MH, Saber PA, Inoshita T, Kamata M, Koike K
    • Journal Title

      Pediatr Blood Cancer

      Volume: 59 Issue: 3 Pages: 461-7

    • DOI

      10.1002/pbc.24055

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Food allergy after cord blood transplantation in children.2012

    • Author(s)
      Sakashita K, Koike K.
    • Journal Title

      Br J Haematol.

      Volume: 158 Issue: 5 Pages: 672-6

    • DOI

      10.1111/j.1365-2141.2012.09204.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] チェルノブイリ原発事故と福島第一原発事故 - 人体への影響 -2012

    • Author(s)
      小池健一
    • Journal Title

      日本小児血液がん学会雑誌

      Volume: 49 Pages: 323-7

    • Related Report
      2012 Annual Research Report
  • [Presentation] Myelodysplastic/myeloproliferative neoplasm in 11 children.2014

    • Author(s)
      Hama A, Manabe A, Koike K, et al
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] International cooperation for Belarus and Iraq2014

    • Author(s)
      Sakashita K, Koike K
    • Organizer
      第117回日本小児科学会学術集会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2014-04-11 – 2014-04-13
    • Related Report
      2014 Annual Research Report
  • [Presentation] 接合菌特異的定量PCRによる接合菌症血清診断法の検討2014

    • Author(s)
      重村倫成、小池 健一、他
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2013 Annual Research Report
  • [Presentation] HLA-DRB1不一致同胞間造血幹細胞移植後に不一致アリルの消失を伴って再発した急性リンパ性白血病の1例2014

    • Author(s)
      倉田 敬、小池 健一、他
    • Organizer
      第36回日本造血細胞移植学会総会
    • Place of Presentation
      沖縄コンベンションセンター
    • Related Report
      2013 Annual Research Report
  • [Presentation] 若年性骨髄単球性白血病に対するGM-CSF受容体を標的とした遺伝子改変T細胞療法の開発2013

    • Author(s)
      中沢 洋三、小池健一、他
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Place of Presentation
      ヒルトン福岡シーホーク
    • Related Report
      2013 Annual Research Report
  • [Presentation] 小児領域のMDS/MPNの分子病態2012

    • Author(s)
      小池健一
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      国立京都国際会館(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] トランスポゾンを用いた慢性肉芽腫症に対する新たな遺伝子治療法の開発2012

    • Author(s)
      重村倫成、中沢洋三、松田和之、小池健一
    • Organizer
      第115回日本小児科学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] 難治性急性リンパ性白血病に対するCD 19特異的遺伝子改変T細胞療2012

    • Author(s)
      斎藤章治, 中沢洋三, 平林耕一, 小池健一, 他
    • Organizer
      第115回日本小児科学会学術集会
    • Place of Presentation
      福岡国際会議場
    • Related Report
      2012 Annual Research Report
  • [Book] ネルソン小児科学2015

    • Author(s)
      中沢洋三、小池健一
    • Total Pages
      4
    • Publisher
      Elsevier
    • Related Report
      2014 Annual Research Report
  • [Book] 今日の治療指針2014

    • Author(s)
      小池健一
    • Total Pages
      2
    • Publisher
      医学書院
    • Related Report
      2014 Annual Research Report
  • [Book] 『今日の診断指針』第7版 小児の貧血2014

    • Author(s)
      小池健一
    • Publisher
      医学書院
    • Related Report
      2013 Annual Research Report
  • [Book] 『今日の治療指針』2014年度版2014

    • Author(s)
      小池健一
    • Publisher
      医学書院
    • Related Report
      2013 Annual Research Report
  • [Book] ネルソン小児科学第19版(翻訳)小児の組織球増殖疾患2014

    • Author(s)
      中沢洋三、小池健一
    • Publisher
      エルゼビアジャパン
    • Related Report
      2013 Annual Research Report
  • [Book] 放射線の子どもへの健康影響2012

    • Author(s)
      小池健一
    • Publisher
      診断と治療社
    • Related Report
      2012 Annual Research Report
  • [Book] 薬剤や放射線障害による貧血2012

    • Author(s)
      小池健一
    • Publisher
      診断と治療社
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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