Establishment of T lymphocytes expressing chimeric antigen receptor for leukemic stem cells
| Project/Area Number |
24390260
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Shinshu University |
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Principal Investigator |
KOIKE Kenichi 信州大学, 学術研究院医学系, 教授 (40143979)
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| 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)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(30 results)
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[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.
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Journal Title
Leukemia
Volume: in press
NAID
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Cytotherapy
Volume: 16
Pages: 1257-69
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Leukemia
Volume: 28
Pages: 1545-8
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Pediatr Blood Cancer
Volume: 61
Pages: 1980-5
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Ann Hematol
Volume: 93
Pages: 949-55
Related Report
Peer Reviewed / Acknowledgement Compliant
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[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.
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Journal Title
Annals of Hematology
Volume: 2014 Jan 25
Related Report
Peer Reviewed
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[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.
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Journal Title
Transfusion
Volume: 54
Issue: 3
Pages: 516-21
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Blood
Volume: 120
Issue: 7
Pages: 1485-1488
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Pediatr Blood Cancer
Volume: 59
Issue: 3
Pages: 461-7
DOI
Related Report
Peer Reviewed
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