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  • 标题:A Chromatographic Approach for Elevating the Antibody-Dependent Cellular Cytotoxicity of Antibody Composites
  • 本地全文:下载
  • 作者:Setsuko Tojo ; Akira Okazaki ; Masako Wakitani
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2009
  • 卷号:32
  • 期号:9
  • 页码:1604-1608
  • DOI:10.1248/bpb.32.1604
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:Recent studies have shown that antibodies with low fucose content in their oligosaccharides exhibit highly potent antibody-dependent cellular cytotoxicity (ADCC). However, composites of therapeutic antibodies produced by conventional production systems using cell lines such as Chinese hamster ovary (CHO) and SP2/0 do not necessarily contain sufficient amounts of non-fucosylated antibody species. In this study, we combined two lectin-affinity chromatography techniques, Concanavalin A and Lens culinaris agglutinin, to enrich the non-fucosylated species from therapeutic material using the anti-Her2/neu model antibody. Oligosaccharide analysis by matrix-assisted laser desorption/ionization-time of flight MS following peptide- N -glycosidase F digestion suggested that non-fucosylated antibody could be enriched in the purified fraction with efficient removal of high-mannose species. The ADCC activity of the purified fraction was about 100-fold higher than that of the initial material. The chromatographic strategy presented here can be a useful tool to elevate ADCC activity of antibody materials without concentrating high-mannose oligosaccharides.
  • 关键词:antibody;lectin;chromatography;antibody-dependent cellular cytotoxicity;fucose;mannose
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