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• W2165170727 endingPage "276" @default.
• W2165170727 startingPage "269" @default.
• W2165170727 abstract "The binding of programmed death ligand 1 protein (PD-L1) to its receptor programmed death protein 1 (PD-1) mediates immunoevasion in cancer and chronic viral infections, presenting an important target for therapeutic intervention. Several monoclonal antibodies targeting the PD-L1/PD-1 signaling axis are undergoing clinical trials; however, the epitopes of these antibodies have not been described. We have combined orthogonal approaches to localize and characterize the epitope of a monoclonal antibody directed against PD-L1 at good resolution and with high confidence. Limited proteolysis and mass spectrometry were applied to reveal that the epitope resides in the first immunoglobulin domain of PD-L1. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to identify a conformational epitope comprised of discontinuous strands that fold to form a beta sheet in the native structure. This beta sheet presents an epitope surface that significantly overlaps with the PD-1 binding interface, consistent with a desired PD-1 competitive mechanism of action for the antibody. Surface plasmon resonance screening of mutant PD-L1 variants confirmed that the region identified by HDX-MS is critical for the antibody interaction and further defined specific residues contributing to the binding energy. Taken together, the results are consistent with the observed inhibitory activity of the antibody on PD-L1-mediated immune evasion. This is the first report of an epitope for any antibody targeting PD-L1 and demonstrates the power of combining orthogonal epitope mapping techniques." @default.
• W2165170727 created "2016-06-24" @default.
• W2165170727 creator A5012796920 @default.
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• W2165170727 creator A5051784579 @default.
• W2165170727 creator A5073325086 @default.
• W2165170727 creator A5074926797 @default.
• W2165170727 date "2015-02-09" @default.
• W2165170727 modified "2023-10-06" @default.
• W2165170727 title "Epitope characterization of an anti-PD-L1 antibody using orthogonal approaches" @default.
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• W2165170727 doi "https://doi.org/10.1002/jmr.2418" @default.
• W2165170727 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25664688" @default.
• W2165170727 hasPublicationYear "2015" @default.
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