MB314 glyco-engineered antibody

 

Antibody mediated effector functions, especially the Antibody Dependent Cellular Cytotoxicity (ADCC) activity, depend on the glycosylation of the IgG Fc-part which interacts with the Fc-gamma receptors (FcyR) expressed on Natural Killer (NK) cells and Monocytes.

Compared to the MB311, MB314 is a second generation product with improved effector functions designed to exert clinical effects via destruction of Lewis Y expressing tumor cells by activation of effector functions and by selective growth inhibition via functional receptors. In MB314, the ADCC effector function has been increased by changing the glycosylation pattern of the parental antibody MB311.

This glyco-engineered variant of the Lewis Y specific humanized antibody MB311 lacking the core fucose residues, show dramatically increased ADCC reactivity on a variety of Lewis Y positive tumor cells as compared to the parental antibody carrying the characteristic core fucosylated N-linked oligosaccharide pattern. Using a glyco-optimized plant expression system - the α1,2-xylosyltransferase and α1,3-fucosyltransferase knockout moss Physcomitrella patens - results in a de-fucosylated antibody (MB314) with up to 40-fold increased ADCC activity. Furthermore it was shown that this increased ADCC activity allows MB314 to overcome the inhibitory effect of endogenous immunoglobulin present in the serum thus further strengthening the potential therapeutic advantage of MB314.

MB314 Fact Sheet