TY  - JOUR
AU  - Deng, Yushuang
AU  - Kumar, Avadh
AU  - Xie, Kan
AU  - Schaaf, Kristina
AU  - Scifo, Enzo
AU  - Morsy, Sarah
AU  - Li, Tao
AU  - Ehninger, Armin
AU  - Bano, Daniele
AU  - Ehninger, Dan
TI  - Targeting senescent cells with NKG2D-CAR T cells.
JO  - Cell death discovery
VL  - 10
IS  - 1
SN  - 2058-7716
CY  - London
PB  - Nature Publishing Group
M1  - DZNE-2024-00538
SP  - 217
PY  - 2024
AB  - This study investigates the efficacy of NKG2D chimeric antigen receptor (CAR) engineered T cells in targeting and eliminating stress-induced senescent cells in vitro. Cellular senescence contributes to age-related tissue decline and is characterized by permanent cell cycle arrest and the senescence-associated secretory phenotype (SASP). Immunotherapy, particularly CAR-T cell therapy, emerges as a promising approach to selectively eliminate senescent cells. Our focus is on the NKG2D receptor, which binds to ligands (NKG2DLs) upregulated in senescent cells, offering a target for CAR-T cells. Using mouse embryonic fibroblasts (MEFs) and astrocytes (AST) as senescence models, we demonstrate the elevated expression of NKG2DLs in response to genotoxic and oxidative stress. NKG2D-CAR T cells displayed potent cytotoxicity against these senescent cells, with minimal effects on non-senescent cells, suggesting their potential as targeted senolytics. In conclusion, our research presents the first evidence of NKG2D-CAR T cells' ability to target senescent brain cells, offering a novel approach to manage senescence-associated diseases. The findings pave the way for future investigations into the therapeutic applicability of NKG2D-targeting CAR-T cells in naturally aged organisms and models of aging-associated brain diseases in vivo.
LB  - PUB:(DE-HGF)16
C6  - pmid:38704364
C2  - pmc:PMC11069534
DO  - DOI:10.1038/s41420-024-01976-7
UR  - https://pub.dzne.de/record/269441
ER  -