Vein-to-Vein Microfluidic Engineering for Cell Therapies
Abraham Lee,
William J. Link Professor and Chair,
University of California-Irvine
Adoptive cell therapy (ACT) involves the processing of blood from a donor to isolate T lymphocytes (T cells) for genetic manipulation followed by reinfusion of the cells into patients. The genetic manipulation is carried out by inserting genetic coding material (e.g. DNA, mRNA) 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. If the cells are from the same patient it is considered autologous and if from a different donor it is allogenic. Also, different immune cells can be used in addition to T cells, e.g., NK cells, dendritic cells, and CD4+ helper T cells. This process that starts from blood from the vein of one person and ends with specialized engineered cells delivered to the vein of a 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 expansion, and cell transfection, and has the potential to drastically reduce cost and processing times. In this presentation, I will introduce our microfluidic platforms based on the lateral cavity acoustic transducer for processing blood samples, isolating T cells, transfecting T cells, and finally expanding T cells to scale up for treatment. The LCAT device has been used to isolate leukocytes from whole blood. In particular, I will introduce the acoustic electric shear orbiting poration (AESOP) device that is able to uniformly deliver genetic cargo dosage into a large population of cells simultaneously in comparison with conventional transfection techniques. I will also introduce an another microfluidic method to construct artificial antigen presenting cells for T cell activation.
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