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@ARTICLE{Deng:269441,
author = {Deng, Yushuang and Kumar, Avadh and Xie, Kan and Schaaf,
Kristina and Scifo, Enzo and Morsy, Sarah and Li, Tao and
Ehninger, Armin and Bano, Daniele and Ehninger, Dan},
title = {{T}argeting senescent cells with {NKG}2{D}-{CAR} {T}
cells.},
journal = {Cell death discovery},
volume = {10},
number = {1},
issn = {2058-7716},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DZNE-2024-00538},
pages = {217},
year = {2024},
abstract = {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.},
cin = {AG Ehninger / AG Bano},
ddc = {610},
cid = {I:(DE-2719)1013005 / I:(DE-2719)1013003},
pnm = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function
(POF4-351)},
pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38704364},
pmc = {pmc:PMC11069534},
doi = {10.1038/s41420-024-01976-7},
url = {https://pub.dzne.de/record/269441},
}