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Folia Pharmacologica Japonica
Article . 2010 . Peer-reviewed
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FcRn, a critical regulator of antibody pharmacokinetics

抗体医薬品の体内動態制御に関わる受容体:FcRn
Authors: Akiko, Ishii-Watabe; Takuo, Suzuki; Minoru, Tada; Toru, Kawanishi; Teruhide, Yamaguchi; Nana, Kawasaki;

FcRn, a critical regulator of antibody pharmacokinetics

Abstract

腫瘍や自己免疫疾患等の治療を目的とした分子標的薬として,抗体医薬品の研究開発が国内外で活発に行われている.抗体医薬品の特徴は標的分子に高い親和性をもって極めて特異的に結合することであるが,他のバイオ医薬品と比較して血中半減期が長いことも特筆すべき点である.ペプチドあるいはタンパク質を医薬品として応用する場合には血中半減期が実用化のためのハードルとなることが少なくない.しかし,多くの抗体医薬品は,生体内IgGの分解抑制に関わるneonatal Fc receptor(FcRn)を介したリサイクリング機構を利用することができるため,数日~数週間という長い血中半減期を有している.FcRnは齧歯類の新生児小腸に高発現し,乳汁に含まれる母親由来IgGの吸収に関与する受容体として同定された.その後の研究により,FcRnが成体においても種々の組織に発現し,IgGのリサイクリングやトランスサイトーシス等に関与していることが報告され,母子免疫以外にも様々な側面でIgGの体内動態制御に関わっていることが明らかにされている.我々は,既承認抗体医薬品のFcRn結合親和性を解析し,ヒトでの血中半減期とFcRn結合親和性の相関,および抗体医薬品のFcRn結合親和性を規定する構造特性の一端を明らかにした.近年の創薬研究では,FcRn結合親和性を改変した抗体医薬品等の開発が進んでいる他,FcRnのもう1つのリガンドであるアルブミンを利用することにより体内動態特性を改変したタンパク質医薬品の開発も進んでいる.FcRnは,抗体医薬品をはじめとするバイオ医薬品の体内動態制御に関わる鍵分子の1つと言えるであろう.

Keywords

Drug Design, Histocompatibility Antigens Class I, Animals, Antibodies, Monoclonal, Humans, Receptors, Fc, Antibodies

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
bronze