Influences of the change of FcRn affinity caused by antibody molecular design on pharmacokinetics.
| Project/Area Number |
18K06776
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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 |
Suzuki Takuo 国立医薬品食品衛生研究所, 生物薬品部, 主任研究官 (10415466)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | FcRn / FcRn親和性改変抗体 / 分布 / 分解 / 体内動態 / ヒトFcRnトランスジェニックマウス / 抗薬物抗体 / Fc融合タンパク質 / Fc gamma受容体 / 抗体医薬品 / 動態 |
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| Outline of Final Research Achievements |
Therapeutic immunoglobulin G (IgG) antibodies have comparatively long half-lives because the neonatal Fc receptor (FcRn) binds to the IgG Fc at acidic pH in the endosome and protects IgG from degradation. Moreover, since FcRn is also considered to play important role in transcytosis of IgGs and trafficking of antigen-bearing IgGs in antigen-presenting cells, the biodistribution and the antigen presentation may be affected by FcRn affinity. In this study, the FcRn-affinity modulated IgGs (adalimumab variants) were injected to human FcRn transgenic mice, and the influence of the FcRn affinity on the biodistribution of IgG was elucidated using the method for distinguishing breakdown products from intact antibodies. Moreover, the production of anti-drug antibody and the biodistribution of the complex of the adalimumab variant with the antigen or anti-drug antibody was analyzed.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、FcRn親和性の違いが臓器分布に及ぼす影響について明らかにすることが出来た。得られた知見は、効果的な抗体医薬品類の分子設計や、FcRn親和性が従来と異なる抗体医薬品の有効性、安全性の評価において重要と考えられる
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Report
(4 results)
Research Products
(3 results)
