Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor

Oncotarget. 2016 Oct 4;7(40):64967-64976. doi: 10.18632/oncotarget.11274.

Abstract

Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value of 1.38 ± 0.39 μM, comparable to the binding affinity of the cognate hPD-L1. A Surface Plasmon Resonance (SPR) competitive binding assay result indicated that Ar5Y_4 could inhibit the interaction of hPD-1/hPD-L1. Moreover, Ar5Y_4 could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Peptides described in this paper provide promising biologic candidates for cancer immunotherapy or diagnostics.

Keywords: de novo peptide design; human programmed death 1; immunotherapy; peptide inhibitor; protein-protein interactions (PPIs).

MeSH terms

  • B7-H1 Antigen / metabolism
  • Carcinoma / immunology
  • Carcinoma / therapy*
  • Computational Biology
  • HCT116 Cells
  • Humans
  • Immunotherapy / methods*
  • Jurkat Cells
  • Lymphocyte Activation
  • Molecular Targeted Therapy
  • Peptides / chemical synthesis
  • Peptides / pharmacology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / metabolism
  • Protein Binding / drug effects
  • Signal Transduction / drug effects
  • Surface Plasmon Resonance
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*

Substances

  • B7-H1 Antigen
  • PDCD1 protein, human
  • Peptides
  • Programmed Cell Death 1 Receptor