Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells.
Cell
; 175(7): 1731-1743.e13, 2018 12 13.
Article
en En
| MEDLINE
| ID: mdl-30503213
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
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Carcinoma de Células Escamosas
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Subfamília C de Receptores Similares a Lectina de Células NK
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Cetuximab
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Antineoplásicos Inmunológicos
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Inmunidad Celular
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Inmunoterapia
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Año:
2018
Tipo del documento:
Article