肿瘤细胞治疗研究
英文原题：Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells.
在嵌合抗原受体（CAR）-T 细胞领域，亟需能够重现实体瘤及肿瘤微环境（TME）挑战的、具有生理相关性的人源模型。
嵌合抗原受体（CAR）T 细胞领域亟需能够模拟实体瘤及肿瘤微环境（TME）挑战的生理相关人体模型。本研究开发了乳腺癌芯片模型，集成内皮屏障，可支持灌注免疫细胞跨内皮迁移、浸润肿瘤，并在灌流培养期间实时监测细胞因子释放，持续最长 8 天。本文示范该模型如何用于研究 CAR-T 疗效及利用药理学开关控制免疫反应。此外，研究将原代乳腺癌类器官整合至模型中，分析患者特异性 CAR-T 疗效。该肿瘤芯片的模块化结构为研究 TME 中其他细胞类型的作用提供了途径，也有望广泛用于实验室至临床转化，并加速 CAR-T 产品的临床前开发。
Physiologically relevant human models that recapitulate the challenges of solid tumors and the tumor microenvironment (TME) are highly desired in the chimeric antigen receptor (CAR)-T cell field. We developed a breast cancer-on-chip model with an integrated endothelial barrier that enables the transmigration of perfused immune cells, their infiltration into the tumor, and concomitant monitoring of cytokine release during perfused culture over a period of up to 8 days. Here, we exemplified its use for investigating CAR-T cell efficacy and the ability to control the immune reaction with a pharmacological on/off switch. Additionally, we integrated primary breast cancer organoids to study patient-specific CAR-T cell efficacy. The modular architecture of our tumor-on-chip paves the way for studying the role of other cell types in the TME and thus provides the potential for broad application in bench-to-bedside translation as well as acceleration of the preclinical development of CAR-T cell products.
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