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Updated: Jan 14, 2026
In Vitro Tumor Cell Rechallenge For Predictive Evaluation of Chimeric Antigen Receptor T Cell Antitumor Function
Published on: February 27, 2019
A tumor-on-a-chip for in vitro study of CAR-T cell immunotherapy in solid tumors
Haijiao Liu1,2, Estela Noguera-Ortega3, Xuanqi Dong1
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
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.
Insights
Researchers developed a novel tumor-on-a-chip system to model chimeric antigen receptor (CAR)-T cell therapy in solid tumors. This microphysiological system enhances understanding of cancer-immune interactions and aids in developing new cancer treatments.
Area of Science:
- Biomedical Engineering
- Cancer Immunology
- Translational Oncology
Background:
- Limited understanding of cancer-immune interactions hinders chimeric antigen receptor (CAR)-T cell therapy for solid tumors.
- Developing effective CAR-T cell therapies requires better models of the tumor microenvironment.
Purpose of the Study:
- To present a microengineered system for vascularized human tumor explants to model CAR-T cell activity.
- To test a chemokine-directed CAR-T cell engineering strategy and identify therapeutic targets for solid malignancies.
Main Methods:
- Development of a microengineered tumor-on-a-chip system with vascularized human tumor explants.
- Controlled perfusion of immune cells to simulate CAR-T cell function in the tumor microenvironment.
- Testing of CAR-T cell engineering strategies and validation in in vivo mouse models; metabolomics analysis.
Main Results:
- Demonstrated the system's ability to simulate, visualize, and interrogate CAR-T cell function in vascularized lung adenocarcinoma.
- Validated a chemokine-directed CAR-T cell engineering strategy in malignant pleural mesothelioma.
- Identified a potential therapeutic target and biomarkers for enhancing CAR-T cell efficacy in lung adenocarcinoma.
Conclusions:
- The microphysiological system offers a promising in vitro technology for advancing adoptive cell therapies.
- This platform can accelerate the development of CAR-T cell therapies for solid tumors and other diseases.
- The study provides insights into cancer-immune interactions and potential therapeutic strategies.
