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dc.contributor.author
Hajduk, Joanna
dc.contributor.author
Brunner, Cyrill
dc.contributor.author
Malik, Sebastian
dc.contributor.author
Bangerter, Jana
dc.contributor.author
Schneider, Gisbert
dc.contributor.author
Thomann, Marco
dc.contributor.author
Reusch, Dietmar
dc.contributor.author
Zenobi, Renato
dc.date.accessioned
2020-03-25T07:57:37Z
dc.date.available
2020-03-24T02:14:39Z
dc.date.available
2020-03-24T12:17:53Z
dc.date.available
2020-03-25T07:57:37Z
dc.date.issued
2020
dc.identifier.issn
1942-0862
dc.identifier.issn
1942-0870
dc.identifier.other
10.1080/19420862.2020.1736975
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/406268
dc.identifier.doi
10.3929/ethz-b-000406268
dc.description.abstract
Minor changes in the quality of biologically manufactured monoclonal antibodies (mAbs) can affect their bioactivity and efficacy. One of the most important variations concerns the N-glycosylation pattern, which directly affects an anti-tumor mechanism called antibody-dependent cell-meditated cytotoxicity (ADCC). Thus, careful engineering of mAbs is expected to enhance both protein-receptor binding and ADCC. The specific aim of this study is to evaluate the influence of terminal carbohydrates within the Fc region on the interaction with the FcγRIIIa/CD16a receptor in native and label-free conditions. The single mAb molecule comprises variants with minimal and maximal galactosylation, as well as α2,3 and α2,6-sialic acid isomers. Here, we apply native electrospray ionization mass spectrometry to determine the solution-phase antibody-receptor equilibria and by using temperature-controlled nanoelectrospray, a thermal stability of the complex is examined. Based on these, we prove that the galactosylation of a fucosylated Fc region increases the binding to CD16a 1.5-fold when compared with the non-galactosylated variant. The α2,6-sialylation has no significant effect on the binding, whereas the α2,3-sialylation decreases it 1.72-fold. In line with expectation, the galactoslylated and α2,6-sialylated mAb:CD16a complex exhibit higher thermal stability when measured in the temperature gradient from 20 to 50°C. The similar binding pattern is observed based on surface plasmon resonance analysis and immunofluorescence staining using natural killer cells. The results of our study provide new insight into N-glycosylation-based interaction of the mAb:CD16a complex.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Taylor & Francis
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc/4.0/
dc.subject
Glycoengineering
en_US
dc.subject
monoclonal antibody
en_US
dc.subject
fc gamma receptor
en_US
dc.subject
native mass spectrometry
en_US
dc.subject
thermal stability
en_US
dc.title
Interaction analysis of glycoengineered antibodies with CD16a: a native mass spectrometry approach
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial 4.0 International
dc.date.published
2020-03-13
ethz.journal.title
mAbs
ethz.journal.volume
12
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
1736975
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Philadelphia, PA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02514 - Laboratorium für Organische Chemie / Laboratory of Organic Chemistry::03430 - Zenobi, Renato / Zenobi, Renato
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03852 - Schneider, Gisbert / Schneider, Gisbert
ethz.relation.isSupplementedBy
10.3929/ethz-b-000388768
ethz.date.deposited
2020-03-24T02:14:44Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2020-03-24T12:18:05Z
ethz.rosetta.lastUpdated
2021-02-15T09:19:00Z
ethz.rosetta.versionExported
true
ethz.COinS
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