Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells,Cell Stem Cell

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Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells
Cell Stem Cell ( IF 19.8 ) Pub Date : 2024-05-15 , DOI: 10.1016/j.stem.2024.04.018
Tengku Ibrahim Maulana ₁ , Claudia Teufel ₂ , Madalena Cipriano ₃ , Julia Roosz ₄ , Lisa Lazarevski ₂ , Francijna E van den Hil ₅ , Lukas Scheller ₆ , Valeria Orlova ₅ , André Koch ₇ , Michael Hudecek ₈ , Miriam Alb ₆ , Peter Loskill ₉

Affiliation

Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.
Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany.
Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany; 3R Center Tübingen for In Vitro Models and Alternatives to Animal Testing, 72074 Tübingen, Germany.
NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands.
Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, 97078 Würzburg, Germany.
Department of Women's Health Tübingen, Eberhard Karls University-Tübingen, 72076 Tübingen, Germany.
Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, 97078 Würzburg, Germany; Fraunhofer-Institut für Zelltherapie und Immunologie IZI, Außenstelle Würzburg Zelluläre Immuntherapie, 97082 Würzburg, Germany.
Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany; 3R Center Tübingen for In Vitro Models and Alternatives to Animal Testing, 72074 Tübingen, Germany.

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.

中文翻译：

用于患者特异性 CAR-T 细胞功效和安全性测试的乳腺癌芯片

嵌合抗原受体 (CAR)-T 细胞领域非常需要能够重现实体瘤和肿瘤微环境 (TME) 挑战的生理相关人体模型。我们开发了一种具有集成内皮屏障的乳腺癌芯片模型，该模型能够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，我们举例说明了其用于研究 CAR-T 细胞功效以及通过药理学开关控制免疫反应的能力。此外，我们整合了原发性乳腺癌类器官来研究患者特异性 CAR-T 细胞的功效。我们的肿瘤芯片的模块化架构为研究其他细胞类型在 TME 中的作用铺平了道路，从而为实验室到临床转化的广泛应用以及加速 CAR 的临床前开发提供了潜力。 T细胞产品。

更新日期：2024-05-15

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