IgG subclass-independent improvement of antibody-dependent cellular cytotoxicity by fucose removal from Asn 297-linked oligosaccharides

• Published in: Journal of immunological methods Vol. 306; no. 1; pp. 151 - 160
• Main Authors: Niwa, Rinpei, Natsume, Akito, Uehara, Aya, Wakitani, Masako, Iida, Shigeru, Uchida, Kazuhisa, Satoh, Mitsuo, Shitara, Kenya
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2005
• Subjects: Antibody oligosaccharide; Antibody-dependent cellular cytotoxicity; Fucose; IgG; CDC; Antibody oligosaccharide; IgG; CHO; ADCC; FcγR; Antibody-dependent cellular cytotoxicity; ELISA; Fucose
• ISSN: 0022-1759; 1872-7905
• DOI: 10.1016/j.jim.2005.08.009

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 FcγRIIIa 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.