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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
De Sousa Linhares A,Battin C,Jutz S,Leitner J,Hafner C,Tobias J,Wiedermann U,Kundi M,Zlabinger GJ,Grabmeier-Pfistershammer K,Steinberger Pdoi
10.1038/s41598-019-47910-1subject
Has Abstractpub_date
2019-08-07 00:00:00pages
11472issue
1issn
2045-2322pii
10.1038/s41598-019-47910-1journal_volume
9pub_type
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