用于 CAR-T 细胞特异性疗效和安全性测试的乳腺癌芯片

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-05-15 DOI:10.1016/j.stem.2024.04.018
Tengku Ibrahim Maulana, Claudia Teufel, Madalena Cipriano, Julia Roosz, Lisa Lazarevski, Francijna E. van den Hil, Lukas Scheller, Valeria Orlova, André Koch, Michael Hudecek, Miriam Alb, Peter Loskill
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引用次数: 0

摘要

嵌合抗原受体(CAR)-T 细胞领域非常需要能再现实体瘤和肿瘤微环境(TME)挑战的生理相关人体模型。我们开发了一种集成了内皮屏障的乳腺癌芯片模型,它能使灌注的免疫细胞迁移、浸润到肿瘤中,并在长达 8 天的灌注培养过程中同时监测细胞因子的释放。在这里,我们举例说明了它在研究 CAR-T 细胞疗效方面的用途,以及通过药理开关控制免疫反应的能力。此外,我们还整合了原发性乳腺癌器官组织来研究患者特异性 CAR-T 细胞的疗效。我们的肿瘤芯片的模块化结构为研究TME中其他细胞类型的作用铺平了道路,从而为从台架到床边的转化提供了广泛的应用潜力,并加速了CAR-T细胞产品的临床前开发。
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Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells

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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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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