利用惯性微流控从白血病血液中富集 T 淋巴细胞以改进 CAR-T 细胞制备

Chimeric antigen receptor cell therapy is a successful immunotherapy for the treatment of blood cancers.

However, hurdles in their manufacturing remain including efficient isolation and purification of the T-cell starting material.

Herein, we describe a one-step separation based on inertial spiral microfluidics for efficient enrichment of T-cells in B-cell acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia patient's samples. In healthy donors used to optimize the process, the lymphocyte purity was enriched from 65% (SD 0. 2) to 91% (SD 0. 06) and T-cell purity was enriched from 45% (SD 0. 1) to 73% (SD 0. 02).

Leukemic samples had higher starting B-cells compared to the healthy donor samples. Efficient enrichment and recovery of lymphocytes and T-cells were achieved in ALL samples with B-cells, monocytes and leukemic blasts depleted by 80% (SD 0. 09), 89% (SD 0. 1) and 74% (SD 0. 09), respectively, and a 70% (SD 0. 1) T-cell recovery. Chronic lymphocytic leukemia samples had lower T-cell numbers, and the separation process was less efficient compared to the ALL.

This study demonstrates the use of inertial microfluidics for T-cell enrichment and depletion of B-cell blasts in ALL, suggesting its potential to address a key bottleneck of the chimeric antigen receptor-T manufacturing workflow.