期刊论文详细信息
Frontiers in Immunology
An Omalizumab Biobetter Antibody With Improved Stability and Efficacy for the Treatment of Allergic Diseases
Peipei Liu1  Su-Jun Deng2  Xueping Wang3  Xiaodan Cao3  Xiaowu Liu3  Haibing Guo3  Dianwen Ju3  Zhongzong Pan3  Jianjian Zhang3  Chunyin Gu3  Zheng Xiao3 
[1] Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China;;Department of Biological Medicines &Shanghai Jemincare Pharmaceuticals Co., Ltd., Shanghai, China;
关键词: IgE;    allergic diseases;    biobetter;    affinity;    stability;    half-life;   
DOI  :  10.3389/fimmu.2020.596908
来源: DOAJ
【 摘 要 】

The critical role of IgE in allergic diseases is well-documented and clinically proven. Omalizumab, a humanized anti-IgE antibody, was the first approved antibody for the treatment of allergic diseases. Nevertheless, omalizumab still has some limitations, such as product instability and dosage restriction in clinical application. In this study, we attempted to develop an omalizumab biobetter antibody with the potential to overcome its limitations. We removed two aspartic acid isomerization hotspots in CDRs of omalizumab to improve antibody candidate’s stability. Meanwhile, several murine amino acids in the framework region of omalizumab were replaced with human source to reduce the potential immunogenicity. Yeast display technology was then applied to screen antibody candidates with high binding affinity to IgE. Moreover, YTE mutation in Fc fragment was introduced into the candidates for extending their serum half-life. A lead candidate, AB1904Am15, was screened out, which showed desired biophysical properties and improved stability, high binding affinity and elevated potency in vitro, prolonged half-life in human FcRn transgenic mouse, and enhanced in vivo efficacy in cynomolgus monkey asthma model. Overall, our study developed a biobetter antibody of omalizumab, AB1904Am15, which has the potential to show improved clinical benefit in the treatment of allergic diseases.

【 授权许可】

Unknown   

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