【摘 要】
：
Monoclonal antibodies produced in mammalian host cells contain an N-linked glycosylation site at Asn 297 of each heavy (two per intact antibody molecule).Glycans on antibodies are typically complex bi
【机 构】
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Early Stage Cell Culture BioProcess Research & Development Genentech Inc.USA
【出 处】
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中国上海第七届国际新药发明科技年会
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Monoclonal antibodies produced in mammalian host cells contain an N-linked glycosylation site at Asn 297 of each heavy (two per intact antibody molecule).Glycans on antibodies are typically complex biatennary structures with very low or no bisecting N-acetylglucosamine and high levels of core fucosylation.Non-fucosylated structures have been shown to be associated with dramatically increased in vitro antibody-dependent cellular cytotoxicity (ADCC) activity leading improved therapeutic protein efficacy possibly.Using small inhibitory RNA (siRNA) technology,we have been able to significantly knock down alpha-l,6-fucosyltransferase (FUT8) resulting in therapeutic antibodies with low fucose content and enhanced Fc receptor binding and enhanced ADCC activity.Using Zinc finger nucleases targeted against FUT8 gene,we developed in-house FUT knockout (FUT8KO) host cells.Antibodies generated from this FUT8KO host are afucosylated.
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