Therapeutic PD-L1 antibodies are more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling

Annika De Sousa Linhares, Claire Battin, Sabrina Jutz, Judith Leitner, Christine Hafner, Joshua Tobias, Ursula Wiedermann, Michael Kundi, Gerhard J Zlabinger, Katharina Grabmeier-Pfistershammer, Peter Steinberger

Research output: Journal article (peer-reviewed)Journal article

71 Citations (Scopus)

Abstract

Inhibitors of PD-1 signaling have revolutionized cancer therapy. PD-1 and PD-L1 antibodies have been approved for the treatment of cancer. To date, therapeutic PD-1 inhibitors have not been compared in a functional assay. We used an efficient T cell reporter platform to evaluate the efficacy of five clinically used PD-1 inhibitors to block PD-1 signaling. The half maximal effective concentrations (EC50) for nivolumab and pembrolizumab were 76.17 ng/ml (95% CI 64.95-89.34 ng/ml) and 39.90 ng/ml (34.01-46.80 ng/ml), respectively. The EC50 values of the PD-L1 inhibitors were 6.46 ng/ml (5.48-7.61 ng/ml), 6.15 ng/ml (5.24-7.21 ng/ml) and 7.64 ng/ml (6.52-8.96 ng/ml) for atezolizumab, avelumab, and durvalumab, respectively. In conclusion, a functional assay evaluating antibodies targeting PD-1 inhibition in vitro revealed that pembrolizumab is a slightly more effective PD-1 blocker than nivolumab, and that PD-L1 antibodies are superior to PD-1 antibodies in reverting PD-1 signaling.

Original languageEnglish
Article number11472
Pages (from-to)11472
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • Animals
  • Antibodies, Monoclonal/pharmacology
  • Antibodies, Monoclonal, Humanized/pharmacology
  • Antineoplastic Agents, Immunological/pharmacology
  • B7-H1 Antigen/antagonists & inhibitors
  • Cell Culture Techniques
  • Coculture Techniques
  • Flow Cytometry
  • Genes, Reporter
  • Green Fluorescent Proteins/chemistry
  • Humans
  • Jurkat Cells
  • Mice
  • Neoplasms/drug therapy
  • Nivolumab/pharmacology
  • Programmed Cell Death 1 Receptor/antagonists & inhibitors
  • Recombinant Proteins/genetics
  • Signal Transduction/drug effects
  • T-Lymphocytes/drug effects

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