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针对TGFβ与嵌合式开关受体和分泌陷以改善T细胞抗瘤活性

Tatyana Matikhina¹, Cyrille J Cohen¹

¹The Laboratory of Tumor Immunology and Immunotherapy, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.

Frontiers in immunology

|November 8, 2024

概括

用新型工程T细胞疗法向转化生长因子β (TGFβ) 增强了抗瘤免疫力. 这些策略改善了瘤微环境中的T细胞功能,为细胞免疫疗法提供了一个有希望的途径.

科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
细胞疗法细胞疗法

背景情况:

转化生长因子β (TGFβ) 是固体瘤中一个关键的免疫抑制因子.
瘤细胞过度表达TGFβ以逃避免疫监测,抑制细胞毒性T细胞活性.
升高的TGFβ水平与瘤入侵和患者预后不佳相关.

研究的目的:

在瘤微环境中开发克服TGFβ介导免疫抑制的策略.
为了增强基因工程T细胞的抗瘤功能.
研究针对TGFβ通路的新型细胞免疫疗法方法.

主要方法:

设计了一种基于TGFβ受体I的协同刺激开关受体 (CSRI),其中包含4-1BB信号部分.
开发了一种T细胞表达的单链可变片段 (scFv) 陷,以结合和中和TGFβ.
共同培养具有黑色素瘤点的工程T细胞,以评估功能改善.

主要成果:

无论是CSRI还是抗TGFβ陷,都增强了瘤特异性的T细胞细胞因子分泌.
观察到T细胞激活标志物的上调和抑制标志物的下调.
工程T细胞在体外和体内都表现出改善的抗瘤活性.

结论:

准TGFβ通路是一种可行的策略,可以提高细胞免疫疗法的疗效.
配备TGFβ抗作用机制的工程T细胞显示出显著的抗瘤潜力.
这些发现支持开发用于TGFβ表达型固体瘤的新型免疫疗法.

关键词:

在T细胞,T细胞.在TCR-T细胞中.在TGF-β的基础上.细胞免疫疗法细胞免疫疗法仿真型的细胞因子受体.

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