Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells

被引：911

作者：

Andre, Pascale ^{[1
]}

Denis, Caroline ^{[1
]}

Soulas, Caroline ^{[1
]}

Bourbon-Caillet, Clarisse ^{[1
]}

Lopez, Julie ^{[1
]}

Arnoux, Thomas ^{[1
]}

Blery, Mathieu ^{[1
]}

Bonnafous, Cecile ^{[1
]}

Gauthier, Laurent ^{[1
]}

Morel, Ariane ^{[1
]}

Rossi, Benjamin ^{[1
]}

Remark, Romain ^{[1
]}

Breso, Violette ^{[1
]}

Bonnet, Elodie ^{[1
]}

Habif, Guillaume ^{[1
]}

Guia, Sophie ^{[2
]}

Lalanne, Ana Ines ^{[3
]}

Hoffmann, Caroline ^{[3
,4
]}

Lantz, Olivier ^{[3
]}

Fayette, Jerome ^{[5
]}

Boyer-Chammard, Agnes ^{[1
]}

Zerbib, Robert ^{[1
]}

Dodion, Pierre ^{[1
]}

Ghadially, Hormas ^{[6
]}

Jure-Kunkel, Maria ^{[7
]}

Morel, Yannis ^{[1
]}

Herbst, Ronald ^{[7
]}

Narni-Mancinelli, Emilie ^{[2
]}

Cohen, Roger B. ^{[8
]}

Vivier, Eric ^{[1
,2
,9
]}

机构：

[1] Innate Pharma, 117 Ave Luminy, F-13009 Marseille, France

[2] Aix Marseille Univ, INSERM, CNRS, Ctr Immunol Marseille Luminy, F-13009 Marseille, France

[3] Inst Curie, INSERM, U932, Immunite & Canc, F-75248 Paris 5, France

[4] Inst Curie, Serv ORL & Chirurg Cervicofaciale, F-75248 Paris 5, France

[5] Ctr Leon Berard, F-69008 Lyon, France

[6] MedImmune Ltd, Aaron Klug Bldg,Granta Pk, Cambridge CB21 6GH, England

[7] MedImmune LLC, One MedImmune Way, Gaithersburg, MD 20878 USA

[8] Abramson Canc Ctr, 3400 Civic Ctr Blvd, West Pavilion, Philadelphia, PA USA

[9] Hop La Timone, AP HP, Serv Immunol, Marseille Immunopole, F-13005 Marseille, France

来源：

CELL | 2018年 / 175卷 / 07期

基金：

欧洲研究理事会;

关键词：

DIFFERENTIAL REGULATION; ACTIVATING RECEPTORS; HLA-E; CANCER; EXPRESSION; LYMPHOCYTES; CD94/NKG2A; CETUXIMAB; EFFICACY; IMMUNOTHERAPY;

D O I：

10.1016/j.cell.2018.10.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Checkpoint inhibitors have revolutionized cancer treatment. However, only a minority of patients respond to these immunotherapies. Here, we report that blocking the inhibitory NKG2A receptor enhances tumor immunity by promoting both natural killer (NK) and CD8(+) T cell effector functions in mice and humans. Monalizumab, a humanized anti-NKG2A antibody, enhanced NK cell activity against various tumor cells and rescued CD8(+) T cell function in combination with PD-x axis blockade. Monalizumab also stimulated NK cell activity against antibody-coated target cells. Interim results of a phase II trial of monalizumab plus cetuximab in previously treated squamous cell carcinoma of the head and neck showed a 31% objective response rate. Most common adverse events were fatigue (17%), pyrexia (13%), and headache (10%). NKG2A targeting with monalizumab is thus a novel checkpoint inhibitory mechanism promoting anti-tumor immunity by enhancing the activity of both T and NK cells, which may complement first-generation immunotherapies against cancer.

引用

页码：1731 / +

页数：26

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