Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity.
Cell
; 177(7): 1701-1713.e16, 2019 06 13.
Article
em En
| MEDLINE
| ID: mdl-31155232
ABSTRACT
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 killer-cell-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. VIDEO ABSTRACT.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
/
Antígenos Ly
/
Anticorpos Biespecíficos
/
Citotoxicidade Imunológica
/
Receptor 1 Desencadeador da Citotoxicidade Natural
/
Antineoplásicos Imunológicos
/
Neoplasias Experimentais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2019
Tipo de documento:
Article