Research on regulatory mechanisms of pharmacodynamics and pharmacokinetics of therapeutic monoclonal antibodies via Fc gamma receptor IIb
| Project/Area Number |
18K06812
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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 47060:Clinical pharmacy-related
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
多田 稔 国立医薬品食品衛生研究所, 生物薬品部, 室長 (50506954)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 抗体医薬品 / Fc受容体 / FcγRIIb / 薬理作用 / 体内動態 / 薬物動態 |
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| Outline of Final Research Achievements |
Based on the recent trends in development of therapeutic antibodies, we performed the study focusing on Fc receptor (FcγRIIb) . The FcγRIIb is an inhibitory receptor that suppresses activation of immune cells by antibodies, and also involved in regulation of pharmacokinetics of antibodies and clearance of antigen-antibody complex. We constructed FcγRIIb and FcγRIIIa co-expressing reporter cells, and showed that the cells are useful for evaluating the FcγRIIb/IIIa activation ratio, which is important in molecular design and evaluation of Fc -modified antibodies. We also constructed a FcγRIIb expressing cell line derived from human hepatic sinusoidal endothelial cells, and suggested that FcγRIIb may be involved in the uptake and toxicity of molecular variants of antibody-drug conjugates.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトFc受容体ファミリーの中で唯一の抑制性受容体であるFcγRIIbが関与する抗体医薬品の薬理作用や細胞内取り込み等の評価に活用できる細胞株を構築し，その有用性を示した．樹立した細胞株は，抗体医薬品の有効性・安全性に関わる機序解明のための研究に役立てることができ，学術的な貢献が期待できる．加えて，構築した細胞は，Fc領域を改変した抗体医薬品の分子設計においても有用であり，次世代抗体医薬品の開発の際にも活用可能であることから，社会的意義も十分と考えられる．
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Report
(5 results)
Research Products
(6 results)
