C-terminal lysine clipping of IgG1: impact on binding to human FcγRIIIa and neonatal Fc receptors.
C-terminal lysine clipping
FcRn
FcγRIIIa
affinity chromatography
charge variants
mass spectrometry
monoclonal antibody
surface plasmon resonance
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
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
105730Informations de copyright
Copyright © 2021. Published by Elsevier B.V.