Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/nature20136 |
Targeting cardiac fibrosis with engineered T cells | |
Aghajanian, Haig1,2,3; Kimura, Toru4; Rurik, Joel G.1,2,3; Hancock, Aidan S.1,2,3; Leibowitz, Michael S.5,6; Li, Li1,2,3; Scholler, John7; Monslow, James8; Lo, Albert8; Han, Wei9; Wang, Tao2; Bedi, Kenneth2,4; Morley, Michael P.2,4; Saldana, Ricardo A. Linares1,2,3; Bolar, Nikhita A.1,2,3; McDaid, Kendra2; Assenmacher, Charles-Antoine10; Smith, Cheryl L.1,2,3; Wirth, Dagmar11; June, Carl H.7; Margulies, Kenneth B.2,4; Jain, Rajan1,2,3,4; Pure, Ellen8; Albelda, Steven M.4; Epstein, Jonathan A.1,2,3,4 | |
2019-09-19 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2019 |
卷号 | 573期号:7774页码:430-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Germany |
英文摘要 | Fibrosis is observed in nearly every form of myocardial disease(1). Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure(2). However, clinical interventions and therapies that target fibrosis remain limited(3). Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8(+) T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease. |
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:000486647800053 |
WOS关键词 | FIBROBLAST ACTIVATION PROTEIN ; MOLECULAR-CLONING ; EXPRESSION ; STROMA ; ALPHA |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
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/202683 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Penn, Perelman Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA; 2.Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA; 3.Univ Penn, Perelman Sch Med, Inst Regenerat Med, Philadelphia, PA 19104 USA; 4.Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA; 5.Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA; 6.Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA; 7.Univ Penn, Perelman Sch Med, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA; 8.Univ Penn, Sch Vet Med, Dept Biomed Sci, Philadelphia, PA 19104 USA; 9.Hosp Univ Penn, Echocardiog Lab, 3400 Spruce St, Philadelphia, PA 19104 USA; 10.Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA; 11.Helmholtz Ctr Infect Res, Model Syst Infect & Immun, Braunschweig, Germany |
推荐引用方式 GB/T 7714 | Aghajanian, Haig,Kimura, Toru,Rurik, Joel G.,et al. Targeting cardiac fibrosis with engineered T cells[J]. NATURE,2019,573(7774):430-+. |
APA | Aghajanian, Haig.,Kimura, Toru.,Rurik, Joel G..,Hancock, Aidan S..,Leibowitz, Michael S..,...&Epstein, Jonathan A..(2019).Targeting cardiac fibrosis with engineered T cells.NATURE,573(7774),430-+. |
MLA | Aghajanian, Haig,et al."Targeting cardiac fibrosis with engineered T cells".NATURE 573.7774(2019):430-+. |
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