| Project/Area Number |
16K09882
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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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| Research Field |
Hematology
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
OGAWA Hiroyasu 兵庫医科大学, 医学部, 名誉教授 (80194447)
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| Co-Investigator(Kenkyū-buntansha) |
岡田 昌也 兵庫医科大学, 医学部, 講師 (00309452)
海田 勝仁 兵庫医科大学, 医学部, 助教 (00441254)
井上 貴之 兵庫医科大学, 医学部, 助教 (20441256)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | HLA半合致移植 / 移植片対白血病効果 / 移植片対宿主病 / 白血病 / サイトカイン / GVHD / GVL / GVL効果 / MHC半合致移植 / 造血幹細胞移植学 |
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| Outline of Final Research Achievements |
We developed originally an HLA-haploidentical stem cell transplantation, which exerts a strong graft-versus-leukemia (GVL) effect. To clarify the mechanism, we originally established a haploidentical murine BMT model. Using the model, we showed a prophylactic dexamethasone (Dex) treatment suppressed GVHD with preserving GVL effects. In secondary lymphoid organs that cause GVH reaction, donor T cells grew by antigen-driven proliferation, and Dex suppressed donor T cell proliferation completely through suppressing the activation of dendritic cells. On the other hands, in bone marrow (BM), in which GVL effects occur, donor T cells were found to grow through homeostatic proliferation, which was not affected by Dex. Furthermore, we demonstrated that donor T cells proliferating in the BM had anti-leukemic effects in in-vitro study. In conclusion, we found that the differences in proliferation style of donor T cells resulted in exerting GVL effects not accompanied by GVH reactions.
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| Academic Significance and Societal Importance of the Research Achievements |
HLA半合致移植で高いGVL効果が得られる機序を明らかにすることによって、非寛解期症例にも有効な新しい移植療法の実現が期待され、現在、救命できていない50-60%の治療抵抗性の患者の救命に貢献できるものと考える。HLA半合致移植のGVHDを制御できるということが、現時点で、世界的な造血幹細胞移植の到達地点であるが、本研究では、その先を行き、HLA半合致移植片のアロ免疫の強さに注目し、それを逆手にとり、治療抵抗性血液腫瘍を治そうという新しい発想の研究である。よって、細胞療法の分野で、HLA適合移植からHLA不適合移植への大きなパラダイムシフトをもたらす可能性があると考えている。
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