Development and characterization of a novel anti-IgE monoclonal antibody
Development and characterization of a novel anti-IgE monoclonal antibody
复制标题
新型抗 IgE 单克隆抗体的开发和表征。
DOI：
10.1016/j.bbrc.2010.04.063
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发表时间：
2010-05-14
影响因子：
3.1
通讯作者：
Guo, Yajun
中科院分区：
文献类型：
--
作者：
Qian, Weizhu;Zhang, Xunmin;Guo, Yajun
免疫球蛋白E是负责过敏反应进展的中心大分子介质。奥马珠单抗(Xolair)是一种针对人IgE的Fc epsilon RI结合域的人源化抗IgE单抗，代表了哮喘治疗的新途径。在本研究中，我们利用杂交瘤技术制备了抗人IgE的单抗(7A5)。我们的数据显示，7A5可以抑制游离的IgE分子与受体结合，而不影响已与细胞受体结合的IgE。重要的是，7A5能够抑制IgE诱导的嗜碱性白血病细胞组胺释放。接下来，利用噬菌体展示肽库技术筛选与7A5结合的多肽，得到一个与IgE-Fc C epsilon 3区序列(391)KQR(393)同源的多肽序列基序，进一步表明7A5与合成的含有391KQR393基序的合成肽“(388)KEEKQRN(394)”有特异性结合。7A5的表位位于Fc epsilon RI结合位点附近，提示7A5与IgE的结合可能通过空间位阻而阻断了IgE与受体的结合。抗IgE单抗7A5有望成为治疗变态反应性疾病的药物。(C)2010 Elsevier Inc.保留所有权利。
IgE is the central macromolecular mediator responsible for the progression of allergic reactions. Omalizumab (Xolair) is a humanized monoclonal anti-IgE antibody directed at the Fc epsilon RI-binding domain of human IgE, which represents a novel therapeutic approach in the management of asthma. In this study, we developed a monoclonal antibody (7A5) against human IgE via hybridoma technique. Our data showed that 7A5 could inhibit free IgE molecules to bind to receptors without affecting IgE already bound to cellular receptors. Importantly, 7A5 was able to inhibit IgE-induced histamine release of basophilic leukemia cells. Next, the phage display peptide library technology was employed to select peptides binding to 7A5 and a striking peptide sequence motif was recovered, which is homologous to the sequence (391)KQR(393) within the C epsilon 3 domain of IgE-Fc, Our results further indicated that 7A5 specifically bound to the synthesized peptide "(388)KEEKQRN(394)" containing the 391KQR393 motif in IgE-Fc. The epitope of 7A5 was found to be spatially close to the Fc epsilon RI-binding site, suggesting that 7A5 binding to IgE might block IgE binding to receptors via steric hindrance. The anti-IgE monoclonal antibody 7A5 may have the potential to be developed as a therapeutic agent for the treatment of allergic diseases. (C) 2010 Elsevier Inc. All rights reserved.