@article{4066, keywords = {CAR-T cells, Cancer, cancer immunotherapy, cancer model, organ-on-chip, solid tumor, tumor immunology, Tumor Microenvironment}, author = {Tengku Ibrahim Maulana and Claudia Teufel and Madalena Cipriano and Julia Roosz and Lisa Lazarevski and Francijna E. van den Hil and Lukas Scheller and Valeria Orlova and André Koch and Michael Hudecek and Miriam Alb and Peter Loskill}, title = {Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells}, abstract = {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.}, year = {2024}, journal = {Cell Stem Cell}, volume = {31}, pages = {989-1002.e9}, month = {2024-07-05}, issn = {1934-5909}, url = {https://www.sciencedirect.com/science/article/pii/S1934590924001450}, doi = {10.1016/j.stem.2024.04.018}, }