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Blocking of the PD‐1/PD‐L1 Interaction by a D‐Peptide Antagonist for Cancer Immunotherapy |
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| 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 Prof Cai‐Yun Fu Prof Yuan‐Ming Qi Prof Lei Liu Prof Yan‐Feng Gao |
| Institution: | 1. Tsinghua‐Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China);2. School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China);3. Tsinghua‐Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunobiology, School of Life Medicine, Tsinghua University, Beijing 100084 (China);4. School of Life Sciences, Zhejiang Sci‐Tech University, Hangzhou 310018, Zhejiang Province (China) |
| 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 DPPA‐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 DPPA‐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. |
| Keywords: | antibodies antitumor agents cancer immunotherapy protein chemical synthesis protein– protein interactions |