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

Autor:	Maulana TI; 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., Teufel C; Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany., Cipriano M; 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., Roosz J; NMI Natural and Medical Sciences Institute at the University of Tübingen, 72770 Reutlingen, Germany., Lazarevski L; Department of Microphysiological Systems, Institute of Biomedical Engineering, Faculty of Medicine, Eberhard Karls University-Tübingen, 72074 Tübingen, Germany., van den Hil FE; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands., Scheller L; Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, 97078 Würzburg, Germany., Orlova V; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden 2333 ZA, the Netherlands., Koch A; Department of Women's Health Tübingen, Eberhard Karls University-Tübingen, 72076 Tübingen, Germany., Hudecek M; 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., Alb M; Medizinische Klinik und Poliklinik II, Lehrstuhl für Zelluläre Immuntherapie, Universitätsklinikum Würzburg, 97078 Würzburg, Germany. Electronic address: alb_m@ukw.de., Loskill P; 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. Electronic address: peter.loskill@uni-tuebingen.de.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Jul 05; Vol. 31 (7), pp. 989-1002.e9. Date of Electronic Publication: 2024 May 15.
DOI:	10.1016/j.stem.2024.04.018
Abstrakt:	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. Competing Interests: Declaration of interests M.H. is an inventor on patent applications and has been granted patents related to CAR technology, licensed in part to industry. M.H. is a cofounder and equity owner of T-CURX GmbH, Würzburg. M.H. receives speaker honoraria from BMS, Janssen, Kite/Gilead, and Novartis and research support from BMS. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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