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通过慢性刺激靶向悬浮培养癌细胞的 CAR 工程化 T 细胞诱导 T 细胞功能障碍

英文原题:Inducing T cell dysfunction by chronic stimulation of CAR-engineered T cells targeting cancer cells in suspension cultures.

查看英文原题

Inducing T cell dysfunction by chronic stimulation of CAR-engineered T cells targeting cancer cells in suspension cultures.

PubMed 2023/01/04(内容时间) STAR Protoc Q4 · IF 1.4(JCR 2025)

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中文摘要

多种临床前模型显示,慢性嵌合抗原受体(CAR)刺激会驱动功能障碍状态,模拟体内治疗失败。本方案介绍如何在悬浮培养中使用表达抗原的癌细胞,对 CAR 工程化 T 细胞进行持续、长期刺激以诱导 T 细胞功能障碍。首先介绍经验证的 CAR-T 制备方法,随后详细说明 CAR-T 慢性刺激方法,以及在慢性刺激过程中评估这些细胞的策略。有关本方案使用和实施的完整细节,请参阅 Singh 等(2020)。

展开英文摘要原文

Several pre-clinical models reveal that chronic chimeric antigen receptor (CAR) stimulation drives a dysfunctional state that mimics in vivo failure. In this protocol, we describe steps to induce T cell dysfunction by persistent and long-term stimulation of CAR-engineered T cells using antigen-expressing cancer cells in suspension cultures.

We first described a validated method for manufacturing of CAR T cells, followed by a detailed method for chronic stimulation of CAR T cells and a strategy to evaluate these cells during the process of chronic stimulation. For complete details on the use and execution of this protocol, please refer to Singh et al. (2020). 1 .

论文信息

作者
Selli ME、Landmann JH、Arveseth C、Singh N
第一作者单位
Washington University School of Medicine, Division of Oncology, St. Louis, MO 63105, USA.United States
通讯作者单位
Washington University School of Medicine, Division of Oncology, St. Louis, MO 63105, USA. Electronic address: nathan.singh@wustl.edu.United States
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
STAR protocols2023 Mar 17
原文标识
PubMed 36607811 · DOI 10.1016/j.xpro.2022.101954