GSTDTAP  > 地球科学
DOI10.1038/s41586-020-2403-9
Senolytic CAR T cells reverse senescence-associated pathologies
Cortez, Jessica T.1,2,3,4; Montauti, Elena5; Shifrut, Eric2,3,4; Gatchalian, Jovylyn6; Zhang, Yusi5; Shaked, Oren2,3,4; Xu, Yuanming5; Roth, Theodore L.1,2,3,4; Simeonov, Dimitre R.1,2,3,4; Zhang, Yana5; Chen, Siqi7; Li, Zhongmei2,3,4; Woo, Jonathan M.2,3,4; Ho, Josephine6; Vogel, Ian A.2,3,4
2020-04-29
发表期刊NATURE
ISSN0028-0836
EISSN1476-4687
出版年2020
卷号583期号:7814页码:127-+
文章类型Article
语种英语
国家USA
英文关键词

Cellular senescence is characterized by stable cell-cycle arrest and a secretory program that modulates the tissue microenvironment(1,2). Physiologically, senescence serves as a tumour-suppressive mechanism that prevents the expansion of premalignant cells(3,4)and has a beneficial role in wound-healing responses(5,6). Pathologically, the aberrant accumulation of senescent cells generates an inflammatory milieu that leads to chronic tissue damage and contributes to diseases such as liver and lung fibrosis, atherosclerosis, diabetes and osteoarthritis(1,7). Accordingly, eliminating senescent cells from damaged tissues in mice ameliorates the symptoms of these pathologies and even promotes longevity(1,2,8-10). Here we test the therapeutic concept that chimeric antigen receptor (CAR) T cells that target senescent cells can be effective senolytic agents. We identify the urokinase-type plasminogen activator receptor (uPAR)(11)as a cell-surface protein that is broadly induced during senescence and show that uPAR-specific CAR T cells efficiently ablate senescent cells in vitro and in vivo. CAR T cells that target uPAR extend the survival of mice with lung adenocarcinoma that are treated with a senescence-inducing combination of drugs, and restore tissue homeostasis in mice in which liver fibrosis is induced chemically or by diet. These results establish the therapeutic potential of senolytic CAR T cells for senescence-associated diseases.


Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescent cells in vitro and in vivo and reduce liver fibrosis in mice.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000541024900011
WOS关键词CELLULAR SENESCENCE ; UROKINASE RECEPTOR ; STELLATE CELLS ; LYMPHOCYTES ; CANCER ; CYTOTOXICITY ; THERAPY ; TUMORS
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
引用统计
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/281560
专题地球科学
资源环境科学
气候变化
作者单位1.Univ Calif San Francisco, Biomed Sci Grad Program, San Francisco, CA 94143 USA;
2.Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA;
3.Univ Calif San Francisco, Diabet Ctr, San Francisco, CA 94143 USA;
4.Univ Calif Berkeley, Innovat Genom Inst, Berkeley, CA 94720 USA;
5.Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA;
6.Salk Inst Biol Studies, Mol & Cellular Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA;
7.Northwestern Univ, Dept Med, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr,Feinberg Sch M, Chicago, IL 60611 USA;
8.Dalian Med Univ, Dept Pharmacol, Sch Pharm, Dalian, Peoples R China;
9.Northwestern Univ, Dept Microbiol & Immunol, Feinberg Sch Med, Chicago, IL 60611 USA;
10.Univ Calif San Francisco, Sean N Parker Autoimmune Res Lab, San Francisco, CA 94143 USA;
11.Parker Inst Canc Immunotherapy, San Francisco, CA 94129 USA;
12.Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA;
13.Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;
14.Chan Zuckerberg Biohub, San Francisco, CA 94158 USA;
15.Univ Calif San Francisco, Rosalind Russell Ephraim P Engleman Rheumatol Res, San Francisco, CA 94143 USA
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GB/T 7714
Cortez, Jessica T.,Montauti, Elena,Shifrut, Eric,et al. Senolytic CAR T cells reverse senescence-associated pathologies[J]. NATURE,2020,583(7814):127-+.
APA Cortez, Jessica T..,Montauti, Elena.,Shifrut, Eric.,Gatchalian, Jovylyn.,Zhang, Yusi.,...&Vogel, Ian A..(2020).Senolytic CAR T cells reverse senescence-associated pathologies.NATURE,583(7814),127-+.
MLA Cortez, Jessica T.,et al."Senolytic CAR T cells reverse senescence-associated pathologies".NATURE 583.7814(2020):127-+.
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