| Project/Area Number |
18K08350
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中沢 洋三 信州大学, 学術研究院医学系, 教授 (60397312)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 若年性骨髄単球性白血病 / iPS細胞 / 分子標的薬 / GMR-CAR-T細胞 / 遺伝子改変T細胞 / 複合治療 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop in-vitro assay using JMML-iPS cells for combination therapy using molecular targeted drug and GMR-CAR-T-cells for JMML. We demonstrated that idelalisib and crizotinib provided cytotoxic effect for PTPN11 gene mutation-positive CD34+ cells derived from JMML-iPS cells. Large amount of CD34+GMR+ cells were shown to be required for development of in-vitro assay for the combination therapy. Therefore, to obtain more the differentiated cells, we need to introduce a gradual increase of cytokines for differentiation and efficient separation of CD34+GMR+ cells.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞株がないJMMLでは、新規治療（薬）の抗腫瘍効果をin-vitroで検証することが困難であった。私たちは、樹立したJMML由来iPS細胞からCD34陽性細胞を分化誘導し、それらの細胞を用いることで、Met阻害剤やPI3K阻害剤がPTPN11変異陽性細胞に、より高い抗腫瘍効果を示すことを明らかにした。GMR-CAR-T細胞と分子標的薬を合わせた複合治療の評価には、多量の分化細胞が必要であることも示した。今後、効率的にiPS細胞から分化細胞を得る工夫を行えば、in-vitroモデルとして新規治療（薬）を評価できる有用なツールになり、難治性のJMMLの治療成績向上に寄与できると考えられる。
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