Development of novel therapeutic strategy against CNS leukemia
| Project/Area Number |
17K16251
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
Kato Itaru 京都大学, 医学研究科, 助教 (10610454)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | 中枢神経白血病 / 低酸素領域 / CART細胞療法 / VEGFA / 低酸素 / bevacizumab / CART療法 / 白血病 / 中枢神経浸潤 / 微小環境 / 代謝 |
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| Outline of Final Research Achievements |
The central nervous system (CNS) is a key site of extramedullary disease in acute lymphoblastic leukemia (ALL). In this study, we investigated the detailed phenotypic, genetic, and transcriptional biology of leukemic cells reside in the CNS. With primary human B-ALL cells and xenograft recipients of primary samples, we demonstrate that leukemic cells that have infiltrated the CNS show features of adaptation to hypoxia and molecular targeted therapy specifically reduces the burden of CNS disease in a xenograft model. Furthermore, we demonstrated a possible novel therapeutic approach against CNS leukemia with CART cells.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床でその治療戦略に難渋することが多く、特に小児患者においては治癒したとしても長期合併症を負った場合には著しいQOLの低下を来すことのある中枢神経浸潤白血病に対して、免疫不全マウスでの細胞増殖の長所を生かして多角的解析を行うことが出来た。明らかにした中枢神経浸潤白血病の特徴を標的とした分子標的による合併症の軽減が期待される新規治療戦略や、がん免疫療法を発展的に使用した治療コンセプトを、マウスを用いた前臨床試験として提示すことが出来た。
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Report
(5 results)
Research Products
(37 results)
