Characterization of multivalent complexes formed in the presence of more than one conventional antibody to terminal complement component C5

Author:

Cone Josh,Kimmel Lida,Zhang Yuchun,Johnson Krista,Sheridan Douglas,Tamburini PaulORCID

Abstract

This study sought to understand the nature of the immune complexes that could be formed when a patient is exposed simultaneously to two different anti-complement component 5 (C5) antibodies, such as in patients converting from one bivalent, noncompetitive, C5-binding monoclonal antibody to another. Size exclusion chromatography (SEC) in combination with multiangle light scattering was used to assess the potential formation of multivalent complexes among eculizumab, C5, and each of two other anti-C5 bivalent antibodies, TPP-2799 or TP-3544, respectively having the same sequence as either crovalimab or pozelimab currently undergoing clinical trials. Each of these two antibodies bound C5 noncompetitively with eculizumab. In phosphate-buffered saline (PBS), C5-eculizumab in the absence of other antibodies measured <500 kDa; however, inclusion of other antibodies at levels ranging from equimolar and up to a fivefold excess over eculizumab and C5 yielded a series of complexes with some >1500 kDa in size, consistent with incorporation of multiple antibodies and C5 molecules. A similar pattern of complexes was also observed when fluorescently labeled eculizumab and either of the other two antibodies were spiked into human plasma, based on SEC monitored by fluorescence detection. A detailed characterization of the pharmacodynamic and pharmacokinetic properties of such complexes is warranted, as is the incorporation of mitigation processes to avoid their formation in patients converting from one bivalent, noncompetitive, C5-binding monoclonal antibody to another.

Funder

Alexion, AstraZeneca Rare Diseas

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3