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

Scientific Reports
Annika De Sousa LinharesPeter Steinberger

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.

References

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Citations

Mar 3, 2020·Biomedit︠s︡inskai︠a︡ khimii︠a︡·E I OlekhnovichE N Ilina
Dec 2, 2020·International Journal of Molecular Sciences·Kevinn Eddy, Suzie Chen
Feb 19, 2020·Cancer Research·Ha-Ram ChaSelvarangan Ponnazhagan
Aug 13, 2020·Oncology Reviews·Giuseppe Luigi BannaAlfredo Addeo
Oct 29, 2020·Communications Biology·Brell JenniferJohannes Stöckl
Mar 18, 2021·Clinical & Translational Immunology·Marie-Laure ClénetNathalie Arbour
May 7, 2021·European Journal of Immunology·Judith LeitnerPeter Steinberger
Apr 4, 2021·Cancer Discovery·Timothy A YapHussein A Tawbi
Aug 14, 2021·Surgery Open Science·Nicholas J SkertichMary Beth Madonna
Oct 21, 2021·Current Opinion in Oncology·Yi-Ze Li, Hong-Mei Zhang

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Methods Mentioned

BETA
flow cytometry

Software Mentioned

GraphPad Prism
CellQuest
GraphPad
FlowJo

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