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

被引:116
|
作者
Linhares, Annika De Sousa [1 ]
Battin, Claire [1 ]
Jutz, Sabrina [1 ]
Leitner, Judith [1 ]
Hafner, Christine [3 ,4 ]
Tobias, Joshua [5 ]
Wiedermann, Ursula [5 ]
Kundi, Michael [6 ]
Zlabinger, Gerhard J. [2 ]
Grabmeier-Pfistershammer, Katharina [2 ]
Steinberger, Peter [1 ]
机构
[1] Med Univ Vienna, Ctr Pathophysiol, Div Immune Receptors & T Cell Activat, Infectiol, Vienna, Austria
[2] Med Univ Vienna, Inst Immunol, Ctr Pathophysiol Infectiol & Immunol, Div Clin & Expt Immunol, Vienna, Austria
[3] Karl Landsteiner Univ Hlth Sci, Univ Hosp St Polten, Dept Dermatol, St Polten, Austria
[4] Karl Landsteiner Gesell, Karl Landsteiner Inst Dermatol Res, St Polten, Austria
[5] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Inst Specif Prophylaxis & Trop Med, Vienna, Austria
[6] Med Univ Vienna, Ctr Publ Hlth, Inst Environm Hlth, Vienna, Austria
基金
奥地利科学基金会;
关键词
T-CELL-ACTIVATION; DENDRITIC CELLS; BLOCKADE; CANCER; INHIBITORS; LIGANDS;
D O I
10.1038/s41598-019-47910-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页数:9
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