C-terminal lysine clipping of IgG1: impact on binding to human FcγRIIIa and neonatal Fc receptors.


Journal

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
ISSN: 1879-0720
Titre abrégé: Eur J Pharm Sci
Pays: Netherlands
ID NLM: 9317982

Informations de publication

Date de publication:
01 Apr 2021
Historique:
received: 05 11 2020
revised: 12 01 2021
accepted: 18 01 2021
pubmed: 26 1 2021
medline: 22 6 2021
entrez: 25 1 2021
Statut: ppublish

Résumé

Monoclonal antibodies (mAbs) display numerous structural attributes, some of them may impact their safety and/or efficacy profiles. C-terminal lysine clipping is a common phenomenon occurring during the bioproduction of mAbs and leads to variable amounts of final process-related charge variants. If Fc-glycosylation has been by far the most documented critical quality attribute (CQA), the potential impacts of mAb C-terminal lysine content is far less reported, particularly on the ability of these basic variants to bind human Fc receptors. To address this question, three charge variant species having zero (K0), one (K1) and two (K2) C-terminal lysine(s) were isolated with high purity from an in-house human IgG1 by preparative strong-cation exchange (SCX) chromatography. A comprehensive biophysical characterization of these three fractions was undertaken, demonstrating their high similarity in terms of structural homogeneity, with a particular attention paid on their respective N-glycosylation profiles. The binding affinity of the fractions to human FcγRIIIa-Val

Identifiants

pubmed: 33493670
pii: S0928-0987(21)00032-4
doi: 10.1016/j.ejps.2021.105730
pii:
doi:

Substances chimiques

Histocompatibility Antigens Class I 0
Immunoglobulin Fc Fragments 0
Immunoglobulin G 0
Receptors, Fc 0
Receptors, IgG 0
Lysine K3Z4F929H6
Fc receptor, neonatal TW3XAW0RCY

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

105730

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Auteurs

Valegh Faid (V)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France. Electronic address: faidv@lfb.fr.

Yann Leblanc (Y)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France.

Marie Berger (M)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France.

Alexander Seifert (A)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France.

Nicolas Bihoreau (N)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France.

Guillaume Chevreux (G)

Analytical Department, LFB Biotechnologies, 3 avenue des Tropiques, 91958 Courtaboeuf (Les Ulis), France.

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Classifications MeSH