Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.
Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.
复制标题
DOI：
10.1016/j.cell.2018.10.014
复制
发表时间：
2018-12-13
期刊：
影响因子：
64.5
通讯作者：
Vivier E
中科院分区：
文献类型：
--
作者：
André P;Denis C;Soulas C;Bourbon-Caillet C;Lopez J;Arnoux T;Bléry M;Bonnafous C;Gauthier L;Morel A;Rossi B;Remark R;Breso V;Bonnet E;Habif G;Guia S;Lalanne AI;Hoffmann C;Lantz O;Fayette J;Boyer-Chammard A;Zerbib R;Dodion P;Ghadially H;Jure-Kunkel M;Morel Y;Herbst R;Narni-Mancinelli E;Cohen RB;Vivier E
检查点抑制剂使癌症治疗发生了革命性的变化。然而，只有少数患者对这些免疫疗法有反应。在这里，我们报告了阻断抑制性NKG2A受体通过促进自然杀伤(NK)和CD8+T细胞效应器功能在小鼠和人类中增强肿瘤免疫。Monalizumab是人源化的抗NKG2A抗体，与PD-x轴阻断相结合，可增强NK细胞对各种肿瘤细胞的活性，并拯救CD8+T细胞功能。Monalizumab还能刺激NK细胞对抗体包被的靶细胞的活性。莫那珠单抗加西妥昔单抗治疗头颈部鳞状细胞癌的II期试验的中期结果显示，客观有效率为31%。最常见的不良反应是乏力(17%)、发热(13%)和头痛(10%)。因此，以monalizumab为靶点的NKG2A是一种新的检查点抑制机制，通过增强T细胞和NK细胞的活性来促进抗肿瘤免疫，这可能是对第一代抗癌免疫疗法的补充。阻断NKG2A释放T和NK细胞效应器功能联合阻断NKG2A和PD-1轴促进抗肿瘤免疫阻断NKG2A并触发CD16说明了双重检查点疗法阻断NKG2A抑制受体的疗效同时释放T和NK细胞，并证明了与抗EGFR或抗PD-x抗体联合使用的抗肿瘤效果。
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. Blocking NKG2A unleashes both T and NK cell effector functions Combined blocking of the NKG2A and the PD-1 axis promotes anti-tumor immunity Blocking NKG2A and triggering CD16 illustrates the efficacy of dual checkpoint therapy Blocking of the NKG2A inhibitory receptor unleashes both T and NK cells, and demonstrates anti-tumor efficacy in combination with anti-EGFR or with anti-PD-x antibodies.
登录
查看更多内容
影响因子：
64.8
作者：
Manguso RT;Pope HW;Zimmer MD;Brown FD;Yates KB;Miller BC;Collins NB;Bi K;LaFleur MW;Juneja VR;Weiss SA;Lo J;Fisher DE;Miao D;Van Allen E;Root DE;Sharpe AH;Doench JG;Haining WN
通讯作者：
Haining WN
影响因子：
20.3
作者：
Benson, Don M., Jr.;Hofmeister, Craig C.;Farag, Sherif S.
通讯作者：
Farag, Sherif S.
影响因子：
20.3
作者：
Cartron, Guillaume;Watier, Herve
通讯作者：
Watier, Herve
影响因子：
5.8
作者：
Manser, Angela R.;Uhrberg, Markus
通讯作者：
Uhrberg, Markus
影响因子：
15.9
作者：
Mamessier, Emilie;Sylvain, Aude;Olive, Daniel
通讯作者：
Olive, Daniel