Journal
ADVANCED HEALTHCARE MATERIALS
Volume 8, Issue 5, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201900001
Keywords
chimeric antigen receptors; hypoxia; immune checkpoints; immunotherapy; ovarian cancer; solid tumors
Funding
- NIH NIBIB Trailblazer Award [R21EB024748]
- USC Viterbi School of Engineering
- STOP CANCER Marni Levine Memorial Research Career Development Award
- Phi Beta Psi Charity Trust
- Rose Hills Fellowship
- USC Provost Ph.D. Fellowship
- USC Women in Science and Engineering (WiSE) Fellowship
- USC Undergraduate Research Associates Program
- National Cancer Institute at the NIH [P30CA014089]
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Despite its revolutionary success in hematological malignancies, chimeric antigen receptor T (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. A microdevice platform that recapitulates a 3D tumor section with a gradient of oxygen and integrates fluidic channels surrounding the tumor for CAR-T cell delivery is engineered. The 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.
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