Bisecting N-Acetylglucosamine of the N-Glycan of Immunoglobulin G Does Not Affect Binding to Fc Gamma Receptors

ACS Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Monoclonal antibodies (mAb) produced in 1,4-mannosyl-glycoprotein 4-N-acetylglucosaminyltransferase (MGAT3) overexpressing cell lines have superior vitro and vivo activities. The N-glycan of the Fc-region these mAbs increased levels bisecting N-acetylglucosamine (GlcNAc) reduced core-fucosylation. Although a reduction core-fucosylation will improve FcγRIIIa binding antibody-dependent cellular cytotoxicity (ADCC) activity, influence GlcNAc on activities has been difficult to probe. Here, we describe preparation unique series homogeneous glycoforms trastuzumab (Herceptin) with without core-fucose examine comprehensive panel Fcγ receptors. were prepared by treatment wild-type Endo-S2 cleave chitobiose core leave GlcNAc-Fuc that was exposed an α-fucosidase provide trastuzumab-GlcNAc. Glycan oxazolines enzymatic remodeling sialoglycopeptide isolated from egg yolk powder, which employed transglycosylations trastuzumab-GlcNAc trastuzumab-GlcNAc-Fuc catalyzed D184M resulting well-defined glycoforms. As expected, had major effect binding, not influenced presence GlcNAc. It found A2-glycan (GlcNAc2Man3GlcNAc2) modified cannot be core-fucosylated FUT8. Thus, only indirect subsequent ADCC activity inhibiting results described here understanding properties therapeutic monoclonal antibodies.

Language: Английский

Bacterial glycoengineering: Cell-based and cell-free routes for producing biopharmaceuticals with customized glycosylation

Current Opinion in Chemical Biology, Journal Year: 2024, Volume and Issue: 81, P. 102500 - 102500

Published: July 10, 2024

Language: Английский