A variant human IgG1-Fc mediates improved ADCC
2011
Ribosome display was applied to the Fc region of humanimmunoglobulin G (IgG1) to select for improved bindingto human FcgRIIIa, the receptor expressed on humannatural killer cells that mediates antibody-dependent cel-lular cytotoxicity (ADCC). A library of human Fcg1 var-iants was generated using error-prone polymerase chainreaction, and subjected to multiple rounds of ribosomedisplay selection against progressively decreasing concen-trations of soluble human FcgRIIIa, to enrich forimproved binders. Radioimmunoassay and alphascreenanalyses of the aglycosylated IgG-Fc output revealedvariants with improved binding to FcgRIIIa relative towild-type IgG-Fc. Subsequent expression in human(HEK-EBNA) cells generated glycosylated IgGs withmodified activity in ADCC assays. One particularvariant, 125_B01 triggered enhanced ADCC (EC
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