1. Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy.
- Author
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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, and Gao, Yan ‐ Feng
- Subjects
PROTEIN-protein interactions ,CANCER immunotherapy ,MEMBRANE proteins ,APOPTOSIS ,ANTINEOPLASTIC agents ,PEPTIDE synthesis ,CIRCULAR dichroism - 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 μ M in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated thatD 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 FROM AUTHOR]- Published
- 2015
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