Bcl-2 Enhances Chimeric Antigen Receptor T Cell Persistence by Reducing Activation-Induced Apoptosis.
Cancers (Basel)
; 13(2)2021 Jan 08.
Article
en En
| MEDLINE
| ID: mdl-33429845
ABSTRACT
PURPOSE:
To evaluate the potential added value of integrating anti-apoptotic molecules for improving the anti-tumor activity of CAR-T cells.METHODS:
Four small molecules inhibiting apoptosis were tested for their ability to prevent activated induced CAR-T cell death. Five CD20-targeting, CD137 (4-1BB) and CD3ζ integrated CAR-T cells (20BBZ) with constitutively expressed anti-apoptotic genes were established, and we screened out the strongest proliferation enhancer Bcl-2. The memory subtype and the exhaustion markers of CAR-T cells were analyzed. The anti-tumor activities of Bcl-2 integrating CAR-T cells (20BBZ-Bcl-2) were evaluated in vitro and in a mouse xenograft lymphoma model.CONCLUSION:
The 20BBZ-Bcl-2 CAR-T cells showed improved proliferation ability compared to 20BBZ CAR-T cells in vitro. In addition, activation-induced apoptosis was reduced in the 20BBZ-Bcl-2 CAR-T cells. Consistent with the enhanced proliferation in vitro, 20BBZ-Bcl-2 CAR-T cells exhibited improved anti-tumor activity in a mouse xenograft lymphoma model.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Cancers (Basel)
Año:
2021
Tipo del documento:
Article
País de afiliación:
China