CELL INTELLIGENCE · 肿瘤细胞治疗研究

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具有干细胞样特征的组织驻留记忆 CAR-T 细胞对实体瘤和血液瘤显示增强疗效

英文原题：Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors.

查看英文原题

Tissue-resident memory CAR T cells with stem-like characteristics display enhanced efficacy against solid and liquid tumors.

PubMed 2023/05/23（内容时间） Cell Rep Med Q1 · IF 14（JCR 2025）

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技术：CAR-T血液系统恶性肿瘤实体瘤地区：美国
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中文摘要

嵌合抗原受体（CAR）T细胞在治疗血液系统恶性肿瘤方面取得了显著成功，但其在非造血系统癌症中的有效性仍然有限。本研究提出通过修饰调控组织驻留适应和早期记忆分化的表观基因组，来增强CAR-T 细胞在实体瘤中的功能和定位。我们发现，人组织驻留记忆CAR-T 细胞（CAR-T RM）形成的一个关键因素是在多效性细胞因子转化生长因子（TGF-）存在下被激活，该因子通过介导染色质重塑和同时发生的转录变化，强制执行既具有“干性”又具有持续组织驻留的核心程序。这种方法产生了一种实用且临床上可行的体外生产方法，可将外周血T细胞工程化为大量“干样”CAR-T RM细胞，这些细胞对肿瘤相关功能障碍具有抵抗力，具备增强的在原位积聚并快速清除癌细胞的能力，从而实现更有效的免疫治疗。

展开英文摘要原文

Chimeric antigen receptor (CAR) T cells demonstrate remarkable success in treating hematological malignancies, but their effectiveness in non-hematopoietic cancers remains limited.

This study proposes enhancing CAR T cell function and localization in solid tumors by modifying the epigenome governing tissue-residency adaptation and early memory differentiation.

We identify that a key factor in human tissue-resident memory CAR T cell (CAR-T RM ) formation is activation in the presence of the pleotropic cytokine, transforming growth factor (TGF- ), which enforces a core program of both "stemness" and sustained tissue residency by mediating chromatin remodeling and concurrent transcriptional changes.

This approach leads to a practical and clinically actionable in vitro production method for engineering peripheral blood T cells into a large number of "stem-like" CAR-T RM cells resistant to tumor-associated dysfunction, possessing an enhanced ability to accumulate in situ and rapidly eliminate cancer cells for more effective immunotherapy.

论文信息

作者
Jung IY、Noguera-Ortega E、Bartoszek R、Collins SM、Williams E、Davis M、Jadlowsky JK、Plesa G
第一作者单位
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.United States
通讯作者单位
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jfrai@upenn.edu.United States
文献类型
非美国政府资助研究 · 美国 NIH 资助研究
期刊
Cell reports. Medicine2023 Jun 20
原文标识
PubMed 37224816　·　DOI 10.1016/j.xcrm.2023.101053

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