Fucose removal from complex-type oligosaccharide enhances the antibody-dependent cellular cytotoxicity of single-gene-encoded antibody comprising a single-chain antibody linked the antibody constant region

Abstract

Fucose removal from complex-type oligosaccharide of human IgG 1-type antibody results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of fucose removal on effector functions of a single-gene-encoded antibody with an scFv used as the binding domain. We generated both a fucose-negative anti-tumor associated glycoprotein (TAG)-72 scFv-Fc using α-1,6-fucosyltransferase knock-out CHO cells and a highly fucosylated scFv-Fc from parental CHO cells. Expression, assembly and antigen binding activity of the scFv-Fcs were not influenced by fucose removal. The scFv-Fc lacking fucose exhibited significantly more potent FcγRIIIa binding and ADCC compared to highly fucosylated scFv-Fc. These results prove that ADCC enhancement by fucose-removal is effective in not only whole IgG 1, but also scFv-Fc, and thus increases the potential of Fc-fusion proteins as therapeutic candidates.