TY - JOUR
KW - CAR-T cells
KW - Cancer
KW - cancer immunotherapy
KW - cancer model
KW - organ-on-chip
KW - solid tumor
KW - tumor immunology
KW - Tumor Microenvironment
AU - Tengku Ibrahim Maulana
AU - Claudia Teufel
AU - Madalena Cipriano
AU - Julia Roosz
AU - Lisa Lazarevski
AU - Francijna E. van den Hil
AU - Lukas Scheller
AU - Valeria Orlova
AU - André Koch
AU - Michael Hudecek
AU - Miriam Alb
AU - Peter Loskill
AB - 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.
BT - Cell Stem Cell
DA - 2024-07-05
DO - 10.1016/j.stem.2024.04.018
IS - 7
N2 - 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.
PY - 2024
SP - 989
EP - 1002.e9
T2 - Cell Stem Cell
TI - Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells
UR - https://www.sciencedirect.com/science/article/pii/S1934590924001450
VL - 31
Y2 - 2024-08-13
SN - 1934-5909
ER -