title: At least two Fc Neu5Gc residues of monoclonal antibodies are required for binding to anti-Neu5Gc antibody.
abstract: Two non-human glycan epitopes, galactose-α-1,3-galactose (α-gal) and Neu5Gc-α-2-6-galactose (Neu5Gc) have been shown to be antigenic when attached to Fab oligosaccharides of monoclonal antibodies (mAbs) , while α-gal attached to Fc glycans was not. However, the antigenicity of Neu5Gc on the Fc glycans remains unclear in the context that most mAbs carry only Fc glycans. After studying two clinical mAbs carrying significant amounts of Fc Neu5Gc, we show that their binding activity with anti-Neu5Gc antibody resided in a small subset of mAbs carrying two or more Fc Neu5Gc, while mAbs harboring only one Neu5Gc showed no reactivity. Since most Neu5Gc epitopes were distributed singly on the Fc of mAbs, our results suggest that the potential antigenicity of Fc Neu5Gc is low. Our study could be referenced in the process design and optimization of mAb production in murine myeloma cells and in the quality control of mAbs for industries and regulatory authorities.
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Chuanfei
authors.initials: C
authors.lastname: Yu
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Gao
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.|International Joint Cancer Institute, the Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Wormald
authors.affiliation: National Institute for Bioprocessing Reseach and Training, Dublin, ROI.|Bioprocessing Technology Institute, A*Star, Singapore.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology; D002240:Carbohydrate Sequence; D000939:Epitopes / Q000276:immunology*; D005690:Galactose / Q000276:immunology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D009844:Oligosaccharides / Q000276:immunology; D011134:Polysaccharides / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D009844:Oligosaccharides; D011134:Polysaccharides; D005690:Galactose
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