期刊
JOURNAL OF IMMUNOLOGICAL METHODS
卷 306, 期 1-2, 页码 151-160出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jim.2005.08.009
关键词
antibody oligosaccharide; antibody-dependent cellular cytotoxicity; IgG; fucose
Fucose depletion from oligosaccharides of human IgG 1-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 IgG 1, fucose-negative variant of IgG2, IgG3, and IgG4 exhibited enhanced ADCC and Fc gamma RIIIa binding compared with their highly fucosylated counterparts. In contrast, facose 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. (c) 2005 Elsevier B.V. All rights reserved.
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