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采用两步染色方案评估活肿瘤组织中 CAR-T 细胞细胞毒性的离体试验

英文原题:An ex vivo assay to assess CAR T cell cytotoxicity in viable tumor tissues using a two-step staining protocol.

查看英文原题

An ex vivo assay to assess CAR T cell cytotoxicity in viable tumor tissues using a two-step staining protocol.

PubMed 2026/01/28(内容时间) Methods Cell Biol

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中文摘要

嵌合抗原受体(CAR)T细胞疗法在血液系统恶性肿瘤中显示出显著疗效,但由于肿瘤微环境(TME)复杂且肿瘤组织穿透有限,其在实体瘤中的成功仍受限制。为此,我们开发了一种通用的两步染色检测方法,可在活体肿瘤组织中体外及离体评估CAR-T 细胞介导的细胞毒作用。该方法结合检测caspase-3/7活性与肿瘤细胞表型鉴定,可可靠地测定CAR-T 细胞疗效。该检测适用于活组织切片和肿瘤细胞系,并可针对不同肿瘤类型和抗原进行定制。该模型为在具有生理相关性的环境中临床前筛选CAR-T 细胞功能提供了稳健工具。

展开英文摘要原文

Chimeric Antigen Receptor (CAR) T cell therapy has shown remarkable efficacy in hematologic malignancies, yet its success in solid tumors remains limited due to the complexity of the tumor microenvironment (TME) and limited penetration. To address this, we developed a versatile two-step staining assay to assess CAR T cell-mediated cytotoxicity both in vitro and ex vivo on viable tumor tissues.

The method combines detection of caspase-3/7 activity with phenotypic characterization of the tumor cells, offering a reliable readout of CAR T cell efficacy. The assay is compatible with live tissue slices and tumor cell lines, and can be customized for various tumor types and antigens. This model provides a robust tool for preclinical screening of CAR T cell function in physiologically relevant contexts.

论文信息

作者
Rajnpreht I、Vimeux L、Donnadieu E
第一作者单位
Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, Paris, France; Inserm UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancers, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: irena.rajnpreht@inserm.fr.France
通讯作者单位
Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, Paris, France; Inserm UMR 1356, Next-Generation Immuno-Oncology Research and Therapy in Pediatric and Adult Cancers, Gustave Roussy, Université Paris-Saclay, Villejuif, France. Electronic address: emmanuel.donnadieu@inserm.fr.France
期刊
Methods in cell biology2026
原文标识
PubMed 42177042 · DOI 10.1016/bs.mcb.2026.01.017