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DOI | 10.1038/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
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
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 |
推荐引用方式 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-+. |
条目包含的文件 | 条目无相关文件。 |
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