دورية أكاديمية
Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells.
| العنوان: | Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells. |
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| المؤلفون: | 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. |
| المصدر: | Cell stem cell [Cell Stem Cell] 2024 Jul 05; Vol. 31 (7), pp. 989-1002.e9. Date of Electronic Publication: 2024 May 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101311472 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1875-9777 (Electronic) Linking ISSN: 18759777 NLM ISO Abbreviation: Cell Stem Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, MA : Cell Press |
| مواضيع طبية MeSH: | Breast Neoplasms*/pathology , Breast Neoplasms*/immunology , Receptors, Chimeric Antigen*/metabolism , Receptors, Chimeric Antigen*/immunology, Humans ; Female ; Immunotherapy, Adoptive/methods ; Tumor Microenvironment ; T-Lymphocytes/immunology ; Lab-On-A-Chip Devices ; Cell Line, Tumor ; Organoids/pathology |
| مستخلص: | 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.) |
| فهرسة مساهمة: | Keywords: CAR-T cells; cancer; cancer immunotherapy; cancer model; organ-on-chip; solid tumor; tumor immunology; tumor microenvironment |
| المشرفين على المادة: | 0 (Receptors, Chimeric Antigen) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240706 Latest Revision: 20240707 |
| رمز التحديث: | 20240708 |
| DOI: | 10.1016/j.stem.2024.04.018 |
| PMID: | 38754430 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1875-9777 |
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| DOI: | 10.1016/j.stem.2024.04.018 |