Breast cancer-on-chip for patient-specific efficacy and safety testing of CAR-T cells.
Cell Stem Cell
; 31(7): 989-1002.e9, 2024 Jul 05.
Article
em En
| MEDLINE
| ID: mdl-38754430
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores de Antígenos Quiméricos
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha