Assessment of the role of afucosylated glycoforms on the in vitro antibody-dependent phagocytosis activity of an antibody to Aβ aggregates
| Autor: | John Coughlin, Allyson Kwiatkowski, Carl Co, Svetlana Bergelson, An Zhang, Cullen Schmid Mason, Eric Chiao, Sei Kameoka, Thomas Cameron |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Glycosylation
medicine.drug_class Amyloid beta THP-1 Cells Immunology antibody-dependent cell-mediated phagocytosis CHO Cells Monoclonal antibody 03 medical and health sciences Protein Aggregates 0302 clinical medicine Cricetulus Cell surface receptor Report medicine Immunology and Allergy Animals Humans Cytotoxicity Antibody 030304 developmental biology Antibody-dependent cell-mediated cytotoxicity 0303 health sciences Amyloid beta-Peptides biology Chemistry Effector IgG1 Receptors IgG Antibody-Dependent Cell Cytotoxicity phagocytosis Antibodies Monoclonal ADCP In vitro Cell biology amyloid beta afucosylation 030220 oncology & carcinogenesis biology.protein Fc effector function |
| Zdroj: | mAbs article-version (VoR) Version of Record |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | The terminal sugars of Fc glycans can influence the Fc-dependent biological activities of monoclonal antibody therapeutics. Afucosylated N-glycans have been shown to significantly alter binding to FcγRIIIa and affect antibody-dependent cell-mediated cytotoxicity (ADCC). Therefore, in order to maintain and ensure safety and efficacy for antibodies whose predominant mechanism of action (MOA) is ADCC, afucosylation is routinely monitored and controlled within appropriate limits. However, it is unclear how the composition and levels of afucosylated N-glycans can modulate the biological activities for a recombinant antibody whose target is not a cell surface receptor, as is the case with ADCC. The impact of different types and varying levels of enriched afucosylated N-glycan species on the in vitro bioactivities is assessed for an antibody whose target is aggregated amyloid beta (Aβ). While either the presence of complex biantennary or high mannose afucosylated glycoforms significantly increased FcγRIIIa binding activity compared to fucosylated glycoforms, they did not similarly increase aggregated Aβ uptake activity mediated by different effector cells. These experiments suggest that afucosylated N-glycans are not critical for the in vitro phagocytic activity of a recombinant antibody whose target is aggregated Aβ and uses Fc effector function as part of its MOA. |
| Databáze: | OpenAIRE |
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