Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Nature ; 629(8010): 201-210, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38600376

RESUMEN

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma1-4, but the efficacy of CAR T cell therapy in solid tumours has been limited5. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass6-8. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.


Asunto(s)
Proteína Forkhead Box O1 , Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Células Madre , Linfocitos T , Humanos , Ratones , Línea Celular Tumoral , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Mitocondrias/metabolismo , Fenotipo , Receptores Quiméricos de Antígenos/inmunología , Receptores Quiméricos de Antígenos/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/citología , Microambiente Tumoral/inmunología , Células Madre/citología , Células Madre/inmunología , Células Madre/metabolismo , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA