Chen Yu-Hsi, Mirza Mahnoor, Jiang Ruoyu, Lee Abraham P
Department of Biomedical Engineering, University of California, Irvine, California 92697, USA.
Biomicrofluidics. 2024 Dec 18;18(6):064105. doi: 10.1063/5.0231595. eCollection 2024 Dec.
Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening. Our aim is to reduce pro-inflammatory cytokine release associated with CRS by controlling CAR surface density on CAR T cells. We show that CAR expression density can be titrated on the surface of primary T cells using an acoustic-electric microfluidic platform. The platform performs dosage-controlled delivery by uniformly mixing and shearing cells, delivering approximately the same amount of CAR gene coding mRNA into each T cell.
嵌合抗原受体（CAR）T细胞疗法在癌症治疗中显示出前所未有的疗效，尤其是在治疗各种血癌患者方面，最显著的是B细胞急性淋巴细胞白血病。近年来，人们一直在研究CAR T细胞疗法用于治疗其他血液系统恶性肿瘤和实体瘤。尽管CAR T细胞疗法取得了显著成功，但细胞因子释放综合征（CRS）是一种意想不到的副作用，可能危及生命。我们的目标是通过控制CAR T细胞上的CAR表面密度来减少与CRS相关的促炎细胞因子释放。我们表明，使用声电微流控平台可以在原代T细胞表面滴定CAR表达密度。该平台通过均匀混合和剪切细胞来进行剂量控制递送，将大约相同量的CAR基因编码mRNA递送到每个T细胞中。
