| Project/Area Number |
18K19477
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | Osaka University |
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Principal Investigator |
Hosen Naoki 大阪大学, 医学系研究科, 教授 (10456923)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | CAR T細胞療法 / 多発性骨髄腫 / CAR T細胞 / がん / 免疫療法 |
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| Outline of Final Research Achievements |
We targeted integrin αvβ6, a cell membrane protein that is highly expressed in breast cancer and known to undergo structural changes. First, integrinβ6 knockout mice were generated in Balb/c background. A large number of monoclonal antibodies were prepared by immunizing integrinβ6 knockout mice with the mouse-derived cells forcibly expressing human integrinαvβ6 as an antigen. From among them, 7 clones of antibodies that bind to both human and mouse integrin αvβ6 were identified. CAR T cells derived from the seven isolated antibodies. They did not damage normal mouse tissues in vivo, but none of them showed significant antitumor effect.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果からインテグリンαvβ6のような正常組織にも発現している蛋白質を標的としてCAR T細胞を作製しても必ずしも正常組織を傷害しないことは明らかである。一方で、抗腫瘍効果も得られていなかった。我々はこの結果から考えて、臨床応用可能なCAR T細胞を開発するためには、やはり、特に標的蛋白質を絞らないで地道にがん特異性の高い抗体/抗原を探索するしかないと思い直し、様々ながんに対するモノクローナル抗体ライブラリーの作製とその中からのがん特異的抗体の単離を進めており、良いものが取れれば、それに焦点を当てて、次のステップへと進むことにしている。
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