@article{6666,
  keywords = {Biomedical Engineering, cancer immunotherapy, Cancer models, Lab-on-a-chip, Tissue engineering},
  author = {Haijiao Liu and Estela Noguera-Ortega and Xuanqi Dong and Won Dong Lee and Jeehan Chang and Sezin Aday Aydin and Yumei Li and Yonghee Shin and Xinyi Shi and Maria Liousia and Marina C. Martinez and Joshua J. Brotman and Soyeon Kim and Zeyu Chen and Anni Wang and Zirui Ou and Jungwook Paek and Ju Young Park and Aidi Liu and Haonan Hu and Zebin Xiao and Dora Maria Racca and Se-jeong Kim and G. Scott Worthen and Wei Guo and Ellen Puré and Taewook Kang and Joshua D. Rabinowitz and E. John Wherry and Edmund K. Moon and Steven M. Albelda and Dan Dongeun Huh},
  title = {A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors},
  abstract = {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.},
  year = {2025},
  journal = {Nature Biotechnology},
  pages = {1-17},
  month = {2025-10-17},
  issn = {1546-1696},
  url = {https://www.nature.com/articles/s41587-025-02845-z},
  doi = {10.1038/s41587-025-02845-z},
  language = {en},
}