Chen Yu-Hsi, Jiang Ruoyu, Lee Abraham P
bioRxiv. 2023 Mar 15:2023.03.14.532624. doi: 10.1101/2023.03.14.532624.
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 (B-ALL). In recent years, CAR T-cell therapies are being investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, it has unexpected side effects that are potentially life threatening. Here, we demonstrate the delivery of approximately the same amount of CAR gene coding mRNA into each T cell propose an acoustic-electric microfluidic platform to manipulate cell membranes and achieve dosage control via uniform mixing, which delivers approximately the same amount of CAR genes into each T cell. We also show that CAR expression density can be titered on the surface of primary T cells under various input power conditions using the microfluidic platform.
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液癌症患者方面，最显著的是B细胞急性淋巴细胞白血病（B-ALL）。近年来，人们正在研究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，但它有一些潜在危及生命的意外副作用。在这里，我们展示了将大致等量的CAR基因编码mRNA递送至每个T细胞中，提出了一种声电微流控平台来操控细胞膜并通过均匀混合实现剂量控制，该平台可将大致等量的CAR基因递送至每个T细胞中。我们还表明，使用该微流控平台可以在各种输入功率条件下对原代T细胞表面的CAR表达密度进行滴定。
