NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates

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	NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates
	Yang, D; Sun, B; Li, SR; Wei, WW; Liu, XY; Cui, XY; Zhang, XN; Liu, N; Yan, LZ; Deng, YB; Zhao, XD
	2023
发表期刊	SCIENCE TRANSLATIONAL MEDICINE
ISSN	1946-6234
卷号	15 期号:709
摘要	Cellular senescence, characterized by stable cell cycle arrest, plays an important role in aging and age-associated pathologies. Eliminating senescent cells rejuvenates aged tissues and ameliorates age-associated diseases. Here, we identified that natural killer group 2 member D ligands (NKG2DLs) are up-regulated in senescent cells in vitro, regardless of stimuli that induced cellular senescence, and in various tissues of aged mice and nonhuman primates in vivo. Accordingly, we developed and demonstrated that chimeric antigen receptor (CAR) T cells targeting human NKG2DLs selectively and effectively diminish human cells undergoing senescence induced by oncogenic stress, replicative stress, DNA damage, or P16(INK4a) overexpression in vitro. Targeting senescent cells with mouse NKG2D-CAR T cells alleviated multiple aging-associated pathologies and improved physical performance in both irradiated and aged mice. Autologous T cells armed with the human NKG2D CAR effectively delete naturally occurring senescent cells in aged nonhuman primates without any observed adverse effects. Our findings establish that NKG2D-CAR T cells could serve as potent and selective senolytic agents for aging and age-associated diseases driven by senescence.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14114
专题	其他
推荐引用方式 GB/T 7714	Yang, D,Sun, B,Li, SR,et al. NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates[J]. SCIENCE TRANSLATIONAL MEDICINE,2023,15(709).
APA	Yang, D.,Sun, B.,Li, SR.,Wei, WW.,Liu, XY.,...&Zhao, XD.(2023).NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates.SCIENCE TRANSLATIONAL MEDICINE,15(709).
MLA	Yang, D,et al."NKG2D-CAR T cells eliminate senescent cells in aged mice and nonhuman primates".SCIENCE TRANSLATIONAL MEDICINE 15.709(2023).

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