A chromatographic approach for elevating the antibody-dependent cellular cytotoxicity of antibody composites.

Autor: Tojo S; Pharmaceutical Research Center, Kyowa Hakko Kirin Co., Ltd., Asahi-machi, Machida, Tokyo, Japan., Okazaki A, Wakitani M, Shinkawa T, Uchida K, Suzawa T
Jazyk: angličtina
Zdroj: Biological & pharmaceutical bulletin [Biol Pharm Bull] 2009 Sep; Vol. 32 (9), pp. 1604-8.
DOI: 10.1248/bpb.32.1604
Abstrakt: 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.
Databáze: MEDLINE