02036nas a2200373   4500000000100000008004100001260001500042653001600057653001100073653002500084653001700109653001800126653001600144653002100160653002700181100002700208700001900235700002200254700001600276700002000292700002900312700001900341700001900360700001600379700002000395700001500415700001800430245009000448856007200538300001600610490000700626520101500633022001401648       2024                            d  c2024-07-0510aCAR-T cells10aCancer10acancer immunotherapy10acancer model10aorgan-on-chip10asolid tumor10atumor immunology10aTumor Microenvironment1 aTengku Ibrahim Maulana1 aClaudia Teufel1 aMadalena Cipriano1 aJulia Roosz1 aLisa Lazarevski1 aFrancijna E. van den Hil1 aLukas Scheller1 aValeria Orlova1 aAndré Koch1 aMichael Hudecek1 aMiriam Alb1 aPeter Loskill00aBreast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells  uhttps://www.sciencedirect.com/science/article/pii/S1934590924001450  a989-1002.e90 v313 aPhysiologically 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.  a1934-5909