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Engineering the interactions between a plant-produced HIV antibody and human Fc receptors.

Stelter, S; Paul, MJ; Teh, AY-H; Grandits, M; Altmann, F; Vanier, J; Bardor, M; Castilho, A; Allen, RL; Ma, JK-C (2020) Engineering the interactions between a plant-produced HIV antibody and human Fc receptors. Plant Biotechnol J, 18 (2). pp. 402-414. ISSN 1467-7652 https://doi.org/10.1111/pbi.13207
SGUL Authors: Ma, Julian Paul, Mathew John Allen, Rachel Louise Teh, Yi Hui

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Abstract

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.

Item Type: Article
Additional Information: © 2019 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: CD16, CD64, Fc receptor, FcRn, antibody, fucose, glycoengineering, methionine oxidation, molecular pharming, neonatal Fc receptor, plant, antibody, glycoengineering, plant, molecular pharming, fucose, Fc receptor, CD64, CD16, FcRn, neonatal Fc receptor, methionine oxidation, Biotechnology, 10 Technology, 06 Biological Sciences, 11 Medical and Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Plant Biotechnol J
ISSN: 1467-7652
Language: eng
Dates:
DateEvent
10 January 2020Published
10 August 2019Published Online
9 July 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDSir Joseph Hotung Charitable TrustUNSPECIFIED
269110European Research Councilhttp://dx.doi.org/10.13039/501100000781
774078European Commission (Pharma-Factory),UNSPECIFIED
760331European Commission (Newcotiana)UNSPECIFIED
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 31301102
Web of Science ID: WOS:000481387000001
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/111013
Publisher's version: https://doi.org/10.1111/pbi.13207

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