Blocking of the PD‐1/PD‐L1 Interaction by a <scp>D</scp>‐Peptide Antagonist for Cancer Immunotherapy
説明
<jats:title>Abstract</jats:title><jats:p>Blockade of the protein–protein interaction between the transmembrane protein programmed cell death protein 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror‐image phage display, we developed the first hydrolysis‐resistant <jats:sc>D</jats:sc>‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound <jats:sup>D</jats:sup>PPA‐1 could bind PD‐L1 at an affinity of 0.51 μ<jats:sc>M</jats:sc> in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that <jats:sup>D</jats:sup>PPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus <jats:sc>D</jats:sc>‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy.</jats:p>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 54 (40), 11760-11764, 2015-08-10
Wiley