【摘 要】
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Two hallmarks of antibody behavior are tight binding and high specificity for a single antigen.We have applied in vitro selection by phage display to create an antigen-recognition surface that binds t
【机 构】
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Senior Scientist Genentech,Inc. USA
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Two hallmarks of antibody behavior are tight binding and high specificity for a single antigen.We have applied in vitro selection by phage display to create an antigen-recognition surface that binds tightly to two different but related antigens, the receptor tyrosine kinases EGFR and HER3.When the dual-action Fab (DAF) named Fab-DL11f is formatted as a human IgG1 (="MEHD7945A"), it shows interesting and potentially useful pre-clinical behaviors arising from the blockade of receptor signals.We have determined X-ray structures of the complexes between fragments of EGFR and HER3 with Fab-DL1 1 and subjected both antigen and Fab binding sites to functional analysis using mutagenesis.The experimental path taken during in vitro selection and the structural flexibility inherent in the Fab antigen combining site conspire to establish only roughly homologous epitopes on EGFR and HER3.Fab-DL11 contact residues and their contributions to binding energies also differ depending on the antigen.
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