https://scholars.lib.ntu.edu.tw/handle/123456789/621161
標題: | IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms | 作者: | Kuo, Be-Sheng Li, Chao-Hung Chen, Jiun-Bo Shiung, Yu-Yu CHIA-YU CHU Lee, Chih-Hung Liu, Yaw-Jen et al., |
關鍵字: | Allergy; Immunology | 公開日期: | 1-八月-2022 | 出版社: | AMER SOC CLINICAL INVESTIGATION INC | 卷: | 132 | 期: | 15 | 來源出版物: | The Journal of clinical investigation | 摘要: | Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/621161 | ISSN: | 0021-9738 | DOI: | 10.1172/JCI157765 |
顯示於: | 醫學系 |
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