Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity

被引：336

作者：

Gauthier, Laurent ^{[1
]}

Morel, Ariane ^{[1
]}

Anceriz, Nadia ^{[1
]}

Rossi, Benjamin ^{[1
]}

Blanchard-Alvarez, Audrey ^{[1
]}

Grondin, Gwendoline ^{[1
]}

Trichard, Sylvia ^{[1
]}

Cesari, Cedric ^{[1
]}

Sapet, Melody ^{[1
]}

Bosco, Frederic ^{[1
]}

Rispaud-Blanc, Helene ^{[1
]}

Guillot, Franceline ^{[1
]}

Cornen, Stephanie ^{[1
]}

Roussel, Alain ^{[2
]}

Amigues, Beatrice ^{[2
]}

Habif, Guillaume ^{[1
]}

Carague, Flavien ^{[1
]}

Arrufat, Sandrine ^{[1
]}

Remark, Romain ^{[1
]}

Romagne, Francois ^{[3
]}

Morel, Yannis ^{[1
]}

Narni-Mancinelli, Emilie ^{[4
]}

Vivier, Eric ^{[1
,4
,5
]}

机构：

[1] Innate Pharma, Marseille, France

[2] Aix Marseille Univ, Architecture & Fonct Macromol Biol, CNRS, Marseille, France

[3] Aix Marseille Univ, MI mAbs, Marseille, France

[4] Aix Marseille Univ, Ctr Immunol Marseille Luminy, CNRS, INSERM, Marseille, France

[5] Hop La Timone, AP HM, Serv Immunol, Marseille Immunopole, Marseille, France

来源：

CELL | 2019年 / 177卷 / 07期

基金：

欧洲研究理事会;

关键词：

C-RECEPTOR POLYMORPHISMS; NK CELLS; T-CELL; BISPECIFIC ANTIBODY; CANCER; CYTOTOXICITY; CARCINOMA; ACTIVATION; IMMUNOTHERAPY; SURVEILLANCE;

D O I：

10.1016/j.cell.2019.04.041

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：

Over the last decade, various new therapies have been developed to promote anti-tumor immunity. Despite interesting clinical results in hematological malignancies, the development of bispecific killercell-engager antibody formats directed against tumor cells and stimulating anti-tumor T cell immunity has proved challenging, mostly due to toxicity problems. We report here the generation of trifunctional natural killer (NK) cell engagers (NKCEs), targeting two activating receptors, NKp46 and CD16, on NK cells and a tumor antigen on cancer cells. Trifunctional NKCEs were more potent in vitro than clinical therapeutic antibodies targeting the same tumor antigen. They had similar in vivo pharmacokinetics to full IgG antibodies and no off-target effects and efficiently controlled tumor growth in mouse models of solid and invasive tumors. Trifunctional NKCEs thus constitute a new generation of molecules for fighting cancer.

引用

页码：1701 / +

页数：29

共 86 条

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