IL-24 improves efficacy of CAR-T cell therapy by targeting stemness of tumor cells.
Br J Cancer
; 130(8): 1337-1347, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38347092
ABSTRACT
BACKGROUND:
Cancer stem cells (CSCs) induce therapeutic resistance and may be an important barrier to cancer immunotherapy. Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable efficacy in clinical settings. However, CAR-T cell therapy fails in a large proportion of patients, especially in those with solid tumors. It is unclear how CSCs mediate resistance to CAR-T cells, and whether CAR-T cells can more effectively eradicate CSCs.METHODS:
In this study, the effect of CSCs on CAR-T cell therapy was determined using in vitro and in vivo assays. Subsequently, Interleukin-24 (IL-24) was expressed along with CAR in T cells. Further in vitro and in vivo tests were performed to determine the effects of IL-24 on CSCs and CAR-T cell therapy.RESULTS:
IL-24 induced apoptosis in CSCs and contributed to T cell activation, differentiation, and proliferation. CAR.IL-24-T cells inhibited CSC enrichment and exhibited stronger antitumor activity in vitro and in vivo.CONCLUSIONS:
IL-24 helps eliminate CSCs and endows CAR-T cells with improved antitumor reactivity.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interleucinas
/
Receptores Quiméricos de Antígenos
Límite:
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2024
Tipo del documento:
Article
País de afiliación:
China