| Project/Area Number |
17K09933
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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 | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉満 誠 鹿児島大学, 医歯学域医学系, 准教授 (70404530)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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)
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| Keywords | ATL / 抗アポトーシス蛋白 / Bcl-2 / Mcl-1 / 成人T細胞白血病・リンパ腫 / Bcl-2関連蛋白 / 前臨床試験 / 新規治療 |
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| Outline of Final Research Achievements |
A treatment strategy targeting one of anti-apoptotic proteins for Adult T-cell leukemia/lymphoma (ATL) will not be successful since ATL cell lines as well as fresh ATL cells from patients express Bcl-2, Bcl-XL and Mcl-1 proteins. It is confirmed by treating ATL cells using either of a bcl-2 inhibitor, Venetoclax or Mcl-1 inhibitor, S63845 in this study. On the other hand, combination of Venetoclax and S63845 showed robust killing activity against ATL cells at the concentration of showing modest toxicity on peripheral blood mononuclear cells from healthy individuals
This study indicated that dual targeting of Bcl-2 and Mcl-1 will be a promising strategy as novel treatment for ATL. This strategy will be feasible in the near future since Venetoclax has been approved for the treatment of chronic lymphocytic leukemia, and S64315, a similar agent of S63845 is in clinical trial.
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| Academic Significance and Societal Importance of the Research Achievements |
抗アポトーシス蛋白を標的とする治療戦略はATLと同じリンパ系腫瘍である慢性リンパ性白血病で既に実臨床に導入されているほか、他の悪性腫瘍に対しても開発中である。
本研究はわが国特有の難治性疾患であるATLの治療戦略において、単一の抗アポトーシス蛋白の抑制では不十分である可能性が高いが、複数、特にBcl-2とMcl-1を同時に標的とする手段は非常に有望な選択となりうることを示している。しかもこれらを標的とする薬剤は既に臨床応用され、もしくは既に進行中の他疾患に対する開発治験が進行中であり、ATLへの臨床応用のためのハードルが高くないことは大きなメリットである。
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