دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Characterization of multivalent complexes formed in the presence of more than one conventional antibody to terminal complement component C5.
المؤلفون: Cone J; Alexion, AstraZeneca Rare Disease, New Haven, CT, United States of America., Kimmel L; Alexion Pharmaceuticals, Inc., New Haven, CT, United States of America., Zhang Y; Alexion, AstraZeneca Rare Disease, New Haven, CT, United States of America., Johnson K; Alexion, AstraZeneca Rare Disease, New Haven, CT, United States of America., Sheridan D; Alexion Pharmaceuticals, Inc., New Haven, CT, United States of America., Tamburini P; Alexion, AstraZeneca Rare Disease, New Haven, CT, United States of America.
المصدر: PloS one [PLoS One] 2023 Apr 20; Vol. 18 (4), pp. e0284502. Date of Electronic Publication: 2023 Apr 20 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Complement C5* , Hemoglobinuria, Paroxysmal*/drug therapy, Humans ; Complement Activation ; Antibodies, Monoclonal/therapeutic use ; Antigen-Antibody Complex
مستخلص: 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.
Competing Interests: JC, YZ, KJ and PT are employees and shareholders of Alexion, AstraZeneca Rare Disease. PT, KJ and DS are co-inventors on numerous patents and patent applications owned by Alexion, AstraZeneca Rare Disease and/or Alexion Pharmaceuticals, Inc. DS was an employee and shareholder of Alexion Pharmaceuticals, Inc., at the time of study and has received consultancy fees from Alexion, AstraZeneca Rare Disease. DS is now an employee and shareholder of Rallybio. LK was an employee and shareholder of Alexion Pharmaceuticals, Inc., at the time of study. LK is an employee of Arvinas, Inc. and an Arvinas, Inc. shareholder. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2023 Cone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: 0 (Complement C5)
0 (Antibodies, Monoclonal)
0 (Antigen-Antibody Complex)
تواريخ الأحداث: Date Created: 20230420 Date Completed: 20230424 Latest Revision: 20230919
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10118082
DOI: 10.1371/journal.pone.0284502
PMID: 37079521
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0284502