Journal
ADVANCED BIOLOGY
Volume 6, Issue 1, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adbi.202101018
Keywords
CAR-T cell; cryoprotectant; manufacture; microfluidic; purification; viability
Categories
Funding
- Australian Research Council Center of Excellence in Convergent Bio-Nano Science and Technology
- Cell Therapy Manufacturing Cooperative Research Center
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CAR-T cell therapy manufacturing process is complex and costly with potential defects. Inertial microfluidics can effectively increase cell viability, reduce cryoprotectant usage, and maintain CAR-T cell functionality.
Chimeric antigen receptor T (CAR-T) cell therapy is rapidly becoming a frontline cancer therapy. However, the manufacturing process is time-, labor- and cost-intensive, and it suffers from significant bottlenecks. Many CAR-T products fail to reach the viability release criteria set by regulators for commercial cell therapy products. This results in non-recoupable costs for the manufacturer and is detrimental to patients who may not receive their scheduled treatment or receive out-of-specification suboptimal formulation. It is demonstrated here that inertial microfluidics can, within minutes, efficiently deplete nonviable cells from low-viability CAR-T cell products. The percentage of viable cells increases from 40% (SD +/- 0.12) to 71% (SD +/- 0.09) for untransduced T cells and from 51% (SD +/- 0.12) to 71% (SD +/- 0.09) for CAR-T cells, which meets the clinical trials' release parameters. In addition, the processing of CAR-T cells formulated in CryStor yields a 91% reduction in the amount of the cryoprotectant dimethyl sulfoxide. Inertial microfluidic processing has no detrimental effects on the proliferation and cytotoxicity of CAR-T cells. Interestingly, approximate to 50% of T-regulatory and T-suppressor cells are depleted, suggesting the potential for inertial microfluidic processing to tune the phenotypical composition of T-cell products.
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