Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy

• DOI: 10.1002/anie.201506225
• Publication Date: 2015-08-11T01:47:11Z
• Authors: Hao‐Nan Chang; Bei‐Yuan Liu; Yun‐Kun Qi; Yang Zhou; Yan‐Ping Chen; Kai‐Mai Pan; Wen‐Wen Li; Xiu‐Man Zhou; Wei‐Wei Ma; Cai‐Yun Fu; Yuan‐Ming Qi; Lei Liu; Yan‐Feng Gao
• Keywords: Blocking (statistics); Cancer Immunotherapy

Abstract Blockade of the protein–protein interaction between transmembrane protein programmed cell death 1 (PD‐1) and its ligand PD‐L1 has emerged as a promising immunotherapy for treating cancers. Using technology mirror‐image phage display, we developed first hydrolysis‐resistant D ‐peptide antagonists to target PD‐1/PD‐L1 pathway. The optimized compound PPA‐1 could bind at an affinity 0.51 μ M in vitro. A blockade assay cellular level tumor‐bearing mice experiments indicated that also effectively disrupt vivo. Thus may provide novel low‐molecular‐weight drug candidates cancer immunotherapy.