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体外模拟抗原特异性 T 细胞介导的癌细胞杀伤

英文原题:Modelling antigen-specific T cell-mediated killing of cancer cells in vitro.

查看英文原题

Modelling antigen-specific T cell-mediated killing of cancer cells in vitro.

PubMed 2026/01/29(内容时间) Methods Cell Biol

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中文摘要

抗原特异性T细胞反应对于有效清除癌细胞至关重要,并且是T细胞免疫疗法的基础。在此,我们提出了一种体外系统,可模拟抗原特异性T细胞激活和癌细胞杀伤的关键步骤。利用OT-1和P14 T细胞受体(TCR)转基因小鼠品系,我们通过体外用同源肽致敏来生成细胞毒性T淋巴细胞(CTL)。通过慢病毒转导或肽脉冲使癌细胞工程化表达抗原,促进形成可被TCR识别的MHC I类-抗原复合物。随后将这些表达抗原的癌细胞与CTL共培养,以评估抗原特异性细胞毒性。通过评估活细胞的代谢活性来定量癌细胞活力,从而精确测量CTL杀伤效率。由于慢病毒转导和肽脉冲均广泛适用于各种癌细胞模型,该平台为剖析抗原特异性癌细胞-T细胞相互作用和评估免疫治疗策略提供了一个多功能工具。

展开英文摘要原文

Antigen-specific T cell responses are critical for effective cancer cell elimination and serve as the basis for T cell-based immunotherapies.

Here, we present an in vitro system that models key steps of antigen-specific T cell activation and cancer cell killing. Using OT-1 and P14 T cell receptor (TCR) transgenic mouse strains, we generate cytotoxic T lymphocytes (CTLs) through in vitro priming with cognate peptides. Cancer cells are engineered to present antigens via lentiviral transduction or peptide pulsing, facilitating the formation of MHC class I-antigen complexes recognized by the TCRs.

These antigen-expressing cancer cells are then co-cultured with CTLs to assess antigen-specific cytotoxicity. Cancer cell viability is quantified by assessing the metabolic activity of living cells, providing a precise measure of CTL killing efficiency. As both lentiviral transduction and peptide pulsing are broadly applicable to various cancer cell models, this platform offers a versatile tool for dissecting antigen-specific cancer cell-T cell interactions and evaluating immunotherapeutic strategies.

论文信息

作者
Engel H、Sun C
第一作者单位
German Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.Germany
通讯作者单位
German Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld, Heidelberg, Germany; German Cancer Consortium (DKTK), DKFZ, core center Heidelberg, Germany. Electronic address: c.sun@dkfz.de.Germany
期刊
Methods in cell biology2026
原文标识
PubMed 42177055 · DOI 10.1016/bs.mcb.2026.01.025