Study on antibody Fc-glycosylation for optimal effector functions

Abstract

A comprehensive structure-activity relationship study on antibody Fc-glycosylation has been performed using the chimeric anti-SSEA4 antibody chMC813-70 as a model. The α-2,6 sialylated biantennary complex type glycan was identified as the optimal Fc-glycan with significant enhancement in antibody effector functions, including binding to different Fc receptors and ADCC.

figure 1:

a general strategy for in-vitro glycan remodeling through the combined use of endoglycosidase and glycosynthase.

figure 2:

glycoengineered antibodies with homogeneous glycoforms of high mannose, hybrid, and complex types. homogeneous antibodies g8, g11, g17, g18, and g20–24 are prepared using chmc813-70, while all other glycoforms are reported using rituximab.

figure 3:

. adcc activity of selected glycoforms tested against pancreatic adenocarcinoma epithelial cell line (hpac).