Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy. Issue 40 (10th August 2015)

• Record Type: Journal Article
• Authors: Chang, Hao‐Nan; Liu, Bei‐Yuan; Qi, Yun‐Kun; Zhou, Yang; Chen, Yan‐Ping; Pan, Kai‐Mai; Li, Wen‐Wen; Zhou, Xiu‐Man; Ma, Wei‐Wei; Fu, Cai‐Yun; Qi, Yuan‐Ming; Liu, Lei; Gao, Yan‐Feng
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 40(2015)
• Page Start: 11760
• Page End: 11764
• Publication Date: 2015-08-10
• Subjects: antibodies -- antitumor agents -- cancer immunotherapy -- protein chemical synthesis -- protein–protein interactions; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201506225
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 D ‐peptide antagonists to target the PD‐1/PD‐L1 pathway. The optimized compound D PPA‐1 could bind PD‐L1 at an affinity of 0.51 μM in vitro. A blockade assay at the cellular level and tumor‐bearing mice experiments indicated that D PPA‐1 could also effectively disrupt the PD‐1/PD‐L1 interaction in vivo. Thus D ‐peptide antagonists may provide novel low‐molecular‐weight drug candidates for cancer immunotherapy. Abstract : Protein chemical synthesis and mirror‐image phage display were combined to develop a proteolysis‐resistant D ‐peptide antagonist ( D PPA‐1) which targets the immune checkpoint protein PD‐L1 (the ligand for PD‐1, the programmed cell death protein 1). D PPA‐1 was found to inhibit the PD‐1/PD‐L1 protein–protein interaction at the cellular level. IgV=immunoglobulin‐like variable.