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Modulating antibody-dependent cellular cytotoxicity of epidermal growth factor receptor-specific heavy-chain antibodies through hinge engineering.

Immunol. Cell Biol.. 2019-07; 
D'EallCalvin,PonRobert A,RossottiMartin A,KrahnNatalie,SpearmanMaureen,CallaghanDeborah,van FaassenHenk,HussackGreg,StetefeldJörg,ButlerMichael,DurocherYves,ZhangJianbing,HenryKevin A,TanhaJam
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Proteins, Expression, Isolation and Analysis Recombinant human EGFR ectodomain (Cat. No. Z03194; GenScript, Piscataway, NJ) was purified by preparative SEC Get A Quote

摘要

Human IgG1 and IgG3 antibodies (Abs) can mediate Ab-dependent cellular cytotoxicity (ADCC), and engineering of the Ab Fc (point mutation; defucosylation) has been shown to affect ADCC by modulating affinity for FcRγIIIa. In the absence of a C 1 domain, many camelid heavy-chain Abs (HCAbs) naturally bear very long and flexible hinge regions connecting their V H and C 2 domains. To better understand the influence of hinge length and structure on HCAb ADCC, we produced a series of hinge-engineered epidermal growth factor receptor (EGFR)-specific chimeric camelid V H-human Fc Abs and characterized their affinities for recombinant EGFR and FcRγIIIa, their binding to EGFR-positive tumor cells, and their a... More

关键词

antibody,antibody engineering,antibody-dependent cellular cytotoxicity (ADCC),epidermal growth factor receptor (EGFR),hinge,single-domain anti