Identification of new functional region of human IgE using Fab libraries

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08808
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Juntendo University
• Principal Investigator: Ando Tomoaki 順天堂大学, 大学院医学研究科, 助教 (10724669)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: IgE / マスト細胞 / アレルギー / 気管支喘息 / 抗体医薬

Outline of Final Research Achievements

We developed new Fab fragments of antibodies against IgE, which is an important molecule involved in the pathogenesis of allergic diseases. These Fab fragments binds IgE at the sites which are different from the sites bound by conventional antibody drugs. These Fab fragments not only block binding of IgE to its receptors, but also facilitated dissociation of the already bound IgE from its receptors. By elucidating the detailed binding portions, we found new structurally important part for the IgE to stably bind to its receptor. These results would serve as a basis for the development of new antibody drugs targeting human IgE.

Free Research Field

アレルギー

Academic Significance and Societal Importance of the Research Achievements

抗ヒトIgE抗体オマリズマブは気管支喘息、慢性特発性蕁麻疹、花粉症などの治療に役立てられており、IgEのアレルギー疾患における役割は近年ますます注目されているが、オマリズマブは効果を発揮するまでに数週間の期間を要するため、より早期に効果を発揮し、より強力な治療薬の開発が求められている。本研究で開発した抗体Fab断片は、すでに受容体に結合したIgEを解離させる能力が強く、オマリズマブよりも早期に効果を発揮することが期待される。今後の臨床応用が期待される抗体医薬である。