1. Evaluating CAR-T Cell Therapy in a Hypoxic 3D Tumor Model
- Author
-
Kimberly A. Gorrell, Hannah Au, Pin Wang, Bethany M. Jarvis, Elizabeth L. Siegler, Hao Zhou, Hoang P. Ta, Keyue Shen, Gunce E. Cinay, and Yuta Ando
- Subjects
medicine.medical_treatment ,T-Lymphocytes ,Biomedical Engineering ,Cell- and Tissue-Based Therapy ,Receptors, Antigen, T-Cell ,Pharmaceutical Science ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Cell Line ,Biomaterials ,Cell therapy ,Immune system ,In vivo ,Antigens, Neoplasm ,Cell Line, Tumor ,Neoplasms ,medicine ,Tumor Microenvironment ,Humans ,Cytotoxicity ,Hypoxia ,Receptors, Chimeric Antigen ,business.industry ,Immunotherapy ,021001 nanoscience & nanotechnology ,medicine.disease ,Chimeric antigen receptor ,0104 chemical sciences ,Immunosurveillance ,Cancer research ,0210 nano-technology ,Ovarian cancer ,business - Abstract
Despite its revolutionary success in hematological malignancies, chimeric antigen receptor (CAR) T cell therapy faces disappointing clinical results in solid tumors. The poor efficacy has been partially attributed to the lack of understanding in how CAR-T cells function in a solid tumor microenvironment. Hypoxia plays a critical role in cancer progression and immune editing, which potentially results in solid tumors escaping immunosurveillance and CAR-T cell-mediated cytotoxicity. Mechanistic studies of CAR-T cell biology in a physiological environment has been limited by the complexity of tumor-immune interactions in clinical and animal models, as well as by a lack of reliable in vitro models. We have engineered a microdevice platform that recapitulates a three-dimensional tumor section with a gradient of oxygen and integrates fluidic channels surrounding the tumor for CAR-T cell delivery. Our design allows for the evaluation of CAR-T cell cytotoxicity and infiltration in the heterogeneous oxygen landscape of in vivo solid tumors at a previously unachievable scale in vitro.
- Published
- 2019