Engineering the interactions between a plant-produced HIV antibody and human Fc receptors.
CD16
CD64
Fc receptor
FcRn
antibody
fucose
glycoengineering
methionine oxidation
molecular pharming
neonatal Fc receptor
plant
Journal
Plant biotechnology journal
ISSN: 1467-7652
Titre abrégé: Plant Biotechnol J
Pays: England
ID NLM: 101201889
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
12
03
2019
revised:
13
06
2019
accepted:
09
07
2019
pubmed:
14
7
2019
medline:
10
7
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
Plants can provide a cost-effective and scalable technology for production of therapeutic monoclonal antibodies, with the potential for precise engineering of glycosylation. Glycan structures in the antibody Fc region influence binding properties to Fc receptors, which opens opportunities for modulation of antibody effector functions. To test the impact of glycosylation in detail, on binding to human Fc receptors, different glycovariants of VRC01, a broadly neutralizing HIV monoclonal antibody, were generated in Nicotiana benthamiana and characterized. These include glycovariants lacking plant characteristic α1,3-fucose and β1,2-xylose residues and glycans extended with terminal β1,4-galactose. Surface plasmon resonance-based assays were established for kinetic/affinity evaluation of antibody-FcγR interactions, and revealed that antibodies with typical plant glycosylation have a limited capacity to engage FcγRI, FcγRIIa, FcγRIIb and FcγRIIIa; however, the binding characteristics can be restored and even improved with targeted glycoengineering. All plant-made glycovariants had a slightly reduced affinity to the neonatal Fc receptor (FcRn) compared with HEK cell-derived antibody. However, this was independent of plant glycosylation, but related to the oxidation status of two methionine residues in the Fc region. This points towards a need for process optimization to control oxidation levels and improve the quality of plant-produced antibodies.
Identifiants
pubmed: 31301102
doi: 10.1111/pbi.13207
pmc: PMC6953194
doi:
Substances chimiques
HIV Antibodies
0
Immunoglobulin Fc Fragments
0
Polysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
402-414Subventions
Organisme : European Research Council
ID : 269110
Pays : International
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.
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