2. Academic Validation
  3. Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy

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

  • Angew Chem Int Ed Engl. 2015 Sep 28;54(40):11760-4. doi: 10.1002/anie.201506225.
Hao-Nan Chang 1,  Bei-Yuan Liu 2,  Yun-Kun Qi 1,  Yang Zhou 2,  Yan-Ping Chen 2,  Kai-Mai Pan 1,  Wen-Wen Li 2,  Xiu-Man Zhou 2,  Wei-Wei Ma 3,  Cai-Yun Fu 4,  Yuan-Ming Qi 2,  Lei Liu 5,  Yan-Feng Gao 6
Affiliations

Affiliations

  • 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).
  • 5 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). [email protected].
  • 6 School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). [email protected].
PMID: 26259671 DOI: 10.1002/anie.201506225
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.

Keywords

antibodies; antitumor agents; cancer immunotherapy; protein chemical synthesis; protein-protein interactions.

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