title: IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn297-linked oligosaccharides.
abstract: Fucose depletion from oligosaccharides of human IgG1-type antibodies 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 all human IgG subclasses. A panel of anti-CD20 chimeric antibodies having a matched set of human heavy chain subclasses with different fucose contents in their oligosaccharides was constructed using wild-type and fucosyltransferase-knockout Chinese hamster ovary cells as host cells. As found previously for IgG1, fucose-negative variant of IgG2, IgG3, and IgG4 exhibited enhanced ADCC and FcgammaRIIIa binding compared with their highly fucosylated counterparts. In contrast, fucose removal did not affect complement-dependent cytotoxicity (CDC) of any IgGs. Consequently, fucose removal from IgG2 and IgG4 resulted in a unique effector function profile; they had potent ADCC and no CDC. In conclusion fucose depletion can provide a panel of IgGs with enhanced ADCC without an impact on other inherent properties specific for each IgG subclass, such as CDC.
authors.affiliation: Department of Antibody Research, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., 3-6-6 Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Rinpei
authors.initials: R
authors.lastname: Niwa
authors.forename: Akito
authors.initials: A
authors.lastname: Natsume
authors.forename: Aya
authors.initials: A
authors.lastname: Uehara
authors.forename: Masako
authors.initials: M
authors.lastname: Wakitani
authors.forename: Shigeru
authors.initials: S
authors.lastname: Iida
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Uchida
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Satoh
authors.forename: Kenya
authors.initials: K
authors.lastname: Shitara
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000920:Antibody-Dependent Cell Cytotoxicity; D018951:Antigens, CD20 / Q000032:analysis / Q000276:immunology; D001216:Asparagine / Q000737:chemistry; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005643:Fucose / Q000737:chemistry*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology; D009844:Oligosaccharides / Q000737:chemistry*; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; C496124:FCGR3A protein, human; D007074:Immunoglobulin G; D009844:Oligosaccharides; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D005643:Fucose; D000069283:Rituximab; D001216:Asparagine