Inertial Microfluidic Purification of CAR-T-Cell Products.
- Publisher:
- WILEY-V C H VERLAG GMBH
- Publication Type:
- Journal Article
- Citation:
- Adv Biol (Weinh), 2022, 6, (1), pp. e2101018-e2101018
- Issue Date:
- 2022-01-01
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| Filename | Description | Size | |||
|---|---|---|---|---|---|
| Advanced Biology - 2021 - Elsemary - Inertial Microfluidic Purification of CAR‐T‐Cell Products.pdf | 2.25 MB |
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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, ≈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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