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

• Published in: Scientific reports 2019-08, Vol.9 (1), p.11472-9, Article 11472
• Main Authors: De Sousa Linhares, Annika, Battin, Claire, Jutz, Sabrina, Leitner, Judith, Hafner, Christine, Tobias, Joshua, Wiedermann, Ursula, Kundi, Michael, Zlabinger, Gerhard J., Grabmeier-Pfistershammer, Katharina, Steinberger, Peter
• Format: Article
• Language: English
• Subjects: 13; 13/31; 14; 14/35; 631/250/251; 631/250/580; 82; 96; 96/35; Animals; Antibodies; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Cell Culture Techniques; Coculture Techniques; Flow Cytometry; Genes, Reporter; Green Fluorescent Proteins - chemistry; Green Fluorescent Proteins - genetics; Humanities and Social Sciences; Humans; Immunoglobulins; Inhibitors; Jurkat Cells; Lymphocytes T; Mice; Monoclonal antibodies; multidisciplinary; Neoplasms - drug therapy; Neoplasms - immunology; Nivolumab - pharmacology; Nivolumab - therapeutic use; PD-1 protein; PD-L1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; Science; Science (multidisciplinary); Signal Transduction - drug effects; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Targeted cancer therapy
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-47910-1

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 (EC 50 ) 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 EC 50 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.