Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.
Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.
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PD-1和PD-L1抑制剂作为癌症免疫疗法的一种形式的开发：对注册试验和未来考虑的全面综述。
DOI：
10.1186/s40425-018-0316-z
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发表时间：
2018-01-23
影响因子：
10.9
通讯作者：
Salgia R
中科院分区：
文献类型：
--
作者：
Gong J;Chehrazi-Raffle A;Reddi S;Salgia R
早期临床前证据提供了程序性细胞死亡1（PD-1）和程序性死亡配体1（PD-L1）阻断作为癌症免疫治疗的潜在形式的基本原理，因为PD-1/PD-L1轴的激活是肿瘤逃避宿主肿瘤抗原特异性T细胞免疫的机制。研究晚期实体瘤中靶向PD-1和PD-L1的几种人源化单克隆IgG 4抗体的早期研究为开发第一种PD-1抑制剂nivolumab和pembrolizumab铺平了道路，这些药物于2014年获得美国食品药品监督管理局（FDA）批准。FDA批准的这类药物的数量正在迅速增加，其治疗适应症涵盖了一系列恶性肿瘤。本综述的目的是强调迄今为止PD-1和PD-L1抑制剂在癌症治疗中的临床发展。特别是，我们专注于详细介绍FDA批准的抗PD-1和抗PD-L1治疗癌症的注册试验。随着PD-1/PD-L1抑制剂数量的持续增长，预测性生物标志物、耐药机制、超进展因子、治疗持续时间和进展后治疗、免疫相关毒性和临床试验设计是需要进一步考虑的关键概念，以优化这类免疫疗法的抗癌潜力。
Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
23.4
作者：
Escudier, Bernard;Motzer, Robert J.;George, Saby
通讯作者：
George, Saby
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
11.5
作者：
Champiat, Stephane;Dercle, Laurent;Ferte, Charles
通讯作者：
Ferte, Charles