TY - JOUR
KW - Biomedical Engineering
KW - cancer immunotherapy
KW - Cancer models
KW - Lab-on-a-chip
KW - Tissue engineering
AU - Haijiao Liu
AU - Estela Noguera-Ortega
AU - Xuanqi Dong
AU - Won Dong Lee
AU - Jeehan Chang
AU - Sezin Aday Aydin
AU - Yumei Li
AU - Yonghee Shin
AU - Xinyi Shi
AU - Maria Liousia
AU - Marina C. Martinez
AU - Joshua J. Brotman
AU - Soyeon Kim
AU - Zeyu Chen
AU - Anni Wang
AU - Zirui Ou
AU - Jungwook Paek
AU - Ju Young Park
AU - Aidi Liu
AU - Haonan Hu
AU - Zebin Xiao
AU - Dora Maria Racca
AU - Se-jeong Kim
AU - G. Scott Worthen
AU - Wei Guo
AU - Ellen Puré
AU - Taewook Kang
AU - Joshua D. Rabinowitz
AU - E. John Wherry
AU - Edmund K. Moon
AU - Steven M. Albelda
AU - Dan Dongeun Huh
AB - Our limited understanding of cancer–immune interactions remains a critical barrier to advancing chimeric antigen receptor (CAR)-T cell therapy for solid malignancies. Here, we present a microengineered system that enables vascularization of human tumor explants and their controlled perfusion with immune cells to model the activity of CAR-T cells in the tumor microenvironment. Using vascularized human lung adenocarcinoma tumors, we first demonstrate the ability of our tumor-on-a-chip system to simulate, visualize and interrogate CAR-T cell function. We then test a chemokine-directed CAR-T cell engineering strategy in a model of malignant pleural mesothelioma and validate our findings in a matching in vivo mouse model. Finally, we describe a potential therapeutic target that can be pharmacologically modulated to increase the efficacy of CAR-T cells in lung adenocarcinoma, for which we present biomarkers identified by global metabolomics analysis. Our microphysiological system provides promising in vitro technology to advance the development of adoptive cell therapies for cancer and other diseases.
BT - Nature Biotechnology
DA - 2025-10-17
DO - 10.1038/s41587-025-02845-z
LA - en
N2 - Our limited understanding of cancer–immune interactions remains a critical barrier to advancing chimeric antigen receptor (CAR)-T cell therapy for solid malignancies. Here, we present a microengineered system that enables vascularization of human tumor explants and their controlled perfusion with immune cells to model the activity of CAR-T cells in the tumor microenvironment. Using vascularized human lung adenocarcinoma tumors, we first demonstrate the ability of our tumor-on-a-chip system to simulate, visualize and interrogate CAR-T cell function. We then test a chemokine-directed CAR-T cell engineering strategy in a model of malignant pleural mesothelioma and validate our findings in a matching in vivo mouse model. Finally, we describe a potential therapeutic target that can be pharmacologically modulated to increase the efficacy of CAR-T cells in lung adenocarcinoma, for which we present biomarkers identified by global metabolomics analysis. Our microphysiological system provides promising in vitro technology to advance the development of adoptive cell therapies for cancer and other diseases.
PY - 2025
SP - 1
EP - 17
T2 - Nature Biotechnology
TI - A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors
UR - https://www.nature.com/articles/s41587-025-02845-z
Y2 - 2025-12-30
SN - 1546-1696
ER -