A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab

被引:198
作者
Fessas, Petros [1 ]
Lee, Hassal [1 ,2 ]
Ikemizu, Shinji [3 ]
Janowitz, Tobias [4 ,5 ,6 ]
机构
[1] Univ Cambridge, Sch Clin Med, Addenbrookes Hosp, Cambridge, England
[2] MRC Lab Mol Biol, Cambridge, England
[3] Kumamoto Univ, Div Struct Biol, Grad Sch Pharmaceut Sci, Kumamoto, Japan
[4] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge, England
[5] Univ Cambridge, Dept Oncol, Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England
[6] Addenbrookes Hosp, Cambridge CB2 0QQ, England
基金
英国惠康基金;
关键词
Nivolumab; Pembrolizumab; PD-1; T-cell checkpoint; BREAST-CANCER; PHASE-I; ANTIBODY; RECEPTOR; PD-1; THERAPY; B7-H1; CD28; EXPRESSION; CARCINOMA;
D O I
10.1053/j.seminoncol.2017.06.002
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
T-cell checkpoint inhibition has a profound impact on cancer care and the programmed cell death protein 1 (PD-1)-targeted antibodies nivolumab and pembrolizumab have been two of the lead molecules of this therapeutic revolution. Their clinical comparability is a highly relevant topic of discussion, but to a significant degree is a consequence of their molecular properties. Here we provide a molecular, preclinical, and early clinical comparison of the two antibodies, based on the available data and recent literature. We acknowledge the limitations of such comparisons, but suggest that based on the available data, differences in clinical trial outcomes between nivolumab and pembrolizumab are more likely drug-independent than drug-dependent. (C) 2017 The Authors. Published by Elsevier Inc.
引用
收藏
页码:136 / 140
页数:5
相关论文
共 37 条
[1]  
[Anonymous], ANN ONCOL S6
[2]   Coming-of-Age of Antibodies in Cancer Therapeutics [J].
Ayyar, B. Vijayalakshmi ;
Arora, Sushrut ;
O'Kennedy, Richard .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2016, 37 (12) :1009-1028
[3]   B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells [J].
Azuma, Takeshi ;
Yao, Sheng ;
Zhu, Gefeng ;
Flies, Andrew S. ;
Flies, Sarah J. ;
Chen, Lieping .
BLOOD, 2008, 111 (07) :3635-3643
[4]   Trastuzumab causes antibody-dependent cellular cytotoxicity-mediated growth inhibition of submacroscopic JIMT-1 breast cancer xenografts despite intrinsic drug resistance [J].
Barok, Mark ;
Isola, Jorma ;
Palyi-Krekk, Zsuzsanna ;
Nagy, Peter ;
Juhasz, Istvan ;
Vereb, Gyorgy ;
Kauraniemi, Paivikki ;
Kapanen, Anita ;
Tanner, Minna ;
Vereb, Gyorgy ;
Szollosi, Janos .
MOLECULAR CANCER THERAPEUTICS, 2007, 6 (07) :2065-2072
[5]   Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma [J].
Bellmunt, J. ;
de Wit, R. ;
Vaughn, D. J. ;
Fradet, Y. ;
Lee, J. -L. ;
Fong, L. ;
Vogelzang, N. J. ;
Climent, M. A. ;
Petrylak, D. P. ;
Choueiri, T. K. ;
Necchi, A. ;
Gerritsen, W. ;
Gurney, H. ;
Quinn, D. I. ;
Culine, S. ;
Sternberg, C. N. ;
Mai, Y. ;
Poehlein, C. H. ;
Perini, R. F. ;
Bajorin, D. F. .
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (11) :1015-1026
[6]   Approvals in 2016: the march of the checkpoint inhibitors [J].
Blumenthal, Gideon M. ;
Pazdur, Richard .
NATURE REVIEWS CLINICAL ONCOLOGY, 2017, 14 (03) :131-132
[7]   Phase I Study of Single-Agent Anti-Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates [J].
Brahmer, Julie R. ;
Drake, Charles G. ;
Wollner, Ira ;
Powderly, John D. ;
Picus, Joel ;
Sharfman, William H. ;
Stankevich, Elizabeth ;
Pons, Alice ;
Salay, Theresa M. ;
McMiller, Tracee L. ;
Gilson, Marta M. ;
Wang, Changyu ;
Selby, Mark ;
Taube, Janis M. ;
Anders, Robert ;
Chen, Lieping ;
Korman, Alan J. ;
Pardoll, Drew M. ;
Lowy, Israel ;
Topalian, Suzanne L. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (19) :3167-3175
[8]  
Chen LJ, 2014, INT J CLIN EXP PATHO, V7, P6015
[9]   Cancer immunotherapy trial registrations increase exponentially but chronic immunosuppressive glucocorticoid therapy may compromise outcomes [J].
Connell, C. M. ;
Raby, S. ;
Beh, I. ;
Flint, T. R. ;
Williams, E. H. ;
Fearon, D. T. ;
Jodrell, D. I. ;
Janowitz, T. .
ANNALS OF ONCOLOGY, 2017, 28 (07) :1678-1679
[10]  
EMA, 2015, ASS REP KEYTR INT NO