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.
Fucose removal from complex-type oligosaccharide of human IgG1-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 alpha-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 FcgammaRIIIa binding and ADCC compared to highly fucosylated scFv-Fc. These results prove that ADCC enhancement by fucose-removal is effective in not only whole IgG1, but also scFv-Fc, and thus increases the potential of Fc-fusion proteins as therapeutic candidates.
Natsume
Akito
A
Department of Antibody Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
Wakitani
Masako
M
Yamane-Ohnuki
Naoko
N
Shoji-Hosaka
Emi
E
Niwa
Rinpei
R
Uchida
Kazuhisa
K
Satoh
Mitsuo
M
Shitara
Kenya
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D005643:Fucose / Q000737:chemistry*; D005647:Fucosyltransferases / Q000235:genetics; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D009154:Mutation; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D009844:Oligosaccharides; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C047052:tumor-associated antigen 72; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase