Home > Publications Database > Targeting senescent cells with NKG2D-CAR T cells. > print

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100 1 _ |a Deng, Yushuang
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245 _ _ |a Targeting senescent cells with NKG2D-CAR T cells.
260 _ _ |a London
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520 _ _ |a 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.
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700 1 _ |a Kumar, Avadh
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700 1 _ |a Xie, Kan
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700 1 _ |a Schaaf, Kristina
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700 1 _ |a Scifo, Enzo
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700 1 _ |a Morsy, Sarah
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700 1 _ |a Li, Tao
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700 1 _ |a Ehninger, Armin
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700 1 _ |a Bano, Daniele
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700 1 _ |a Ehninger, Dan
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773 _ _ |a 10.1038/s41420-024-01976-7
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