EAGER: A Microscale Testbed to Assay and Manufacture CAR T-Cell Immunotherapies

2016 - presentpresent

Genetically-engineered human T-cells that express chimeric antigen receptors (CARs) have been used to target cancer-associated antigens. While CAR T-cells have had success in treating hematological malignancies, they are only just starting to be used to combat solid tumors. Experimental approaches to functionally assess and isolate immune cells have been performed and are quite promising, yet we lack availability of such tools for the broader research community. We propose to develop a flexible, cost-effective, and scalable microscale co-culture system to isolate functional gene-edited CAR T-cells, expand the fraction, and assess in vivo functionality. This microscale testbed would advance biomanufacturing by (1) defining and reducing variability in cell products in CAR T-cell workflows, (2) generating a rapid, nondestructive characterization of T-cell functionality, and (3) establishing a scalable purification strategy for adoptive and autologous immunotherapies. In the long-term, a robust, microscale testbed could be used to increase the level of cell-intrinsic complexity programmed into immunotherapies by synthetic biologists (e.g., genetic circuits) and the level of cell-extrinsic complexity that can be generated at the microscale by tissue engineers (e.g., incorporation of 3D tumor organoids and microvasculature).