Abstract

Microfluidic T Cell Engineering For Immunotherapies

Abraham Lee, William J. Link Professor and Chair, University of California-Irvine

Adoptive cell therapy (ACT) is a type of immunotherapy that involves the processing of blood from a donor to isolate immune cells (e.g. T cells) for genetic manipulation followed by reinfusion of the cells into patients. Specifically for CAR T cell therapy, genetic coding material (e.g. DNA, mRNA) is inserted into the T cells to express chimeric antigen receptors to target biomarkers of cancer cells and trigger an activated immune response towards the tumor of interest. This process that starts from blood drawn from one person and ends with specialized engineered cells delivered to the same patient includes multiple tedious and costly steps, and can require a long time that the patient may not have. Microfluidics techniques are being developed that can address all steps of this cell manufacturing process, including cell harvesting, cell isolation, cell activation and expansion, and cell transfection. In this talk I will introduce two microfluidic platforms in my lab, one is the lateral cavity acoustic transducer (LCAT) and the other is droplet microfluidics. LCAT was used for processing blood samples, isolating T cells, transfecting T cells, and finally expanding T cells to scale up for treatment. Based on LCAT, we developed the acoustic electric shear orbiting poration (AESOP) device to uniformly deliver genetic cargo dosage into a large population of cells simultaneously. Based on droplet microfluidics we constructed a single cell artificial antigen presenting cells (aAPCs) for T cell activation. By trapping single cells in microfluidic compartments, we are able to study the cell morphology and cell-cell communications to further understand immune cell activation and immune cell synapses.