bioRxivJClub
Asymmetrical Glyco-Engineering of Monoclonal Antibodies Provides Insights into α-Gal Immunogenicity
bioRxiv · · Preprint · Open access
Bosman, Ehlers + 7 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
A two-stage, fully enzymatic platform enables complete control of biantennary mAb Fc glycoforms’ alpha1,3/alpha1,6 arm asymmetry, demonstrated on infliximab and cetuximab.
- Why it matters: Current enzymatic remodeling yields only a narrow glycoform spectrum and cannot fully control defined asymmetrical structures needed to study and optimize Fc effector functions.
- What they did: Using StrH (GH20-2) for regioselective GlcNAc hydrolysis on the alpha1,3-mannose arm, then extending the alpha1,6 antenna with galactoside/sialoside or alpha1,3-galactoside, GnT-I reintroduces GlcNAc for controlled branching.
- The result: The resulting glycovariants define minimum structural requirements for anti-alpha-Gal IgE binding and systematically map binding affinities to FcgammaRs, informing rational design of next-generation immune therapeutics.
The findingWhy it mattersWhat they didThe result
- Open access