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基于微流控的剂量可控胞内 mRNA 递送平台实现的 CAR-T 细胞嵌合抗原受体滴定

英文原题:Titering of Chimeric Antigen Receptors on CAR T Cells enabled by a Microfluidic-based Dosage-Controlled Intracellular mRNA Delivery Platform.

查看英文原题

Titering of Chimeric Antigen Receptors on CAR T Cells enabled by a Microfluidic-based Dosage-Controlled Intracellular mRNA Delivery Platform.

PubMed 2023/03/15(内容时间) bioRxiv

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中文摘要

CAR-T 在癌症治疗、特别是B细胞急性淋巴细胞白血病等血液肿瘤中取得前所未有的疗效,当前也在拓展至其他血液肿瘤和实体瘤,但可能出现危及生命的意外副作用。本研究提出一种声学-电学微流控平台,通过均匀混合和操控细胞膜,使每个T细胞获得近似相同剂量的CAR编码mRNA。研究还显示,可通过改变输入功率调节原代T细胞表面CAR表达密度。

展开英文摘要原文

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.

论文信息

作者
Chen YH、Jiang R、Lee AP
文献类型
预印本
期刊
bioRxiv : the preprint server for biology2023 Mar 15
原文标识
PubMed 36993279 · DOI 10.1101/2023.03.14.532624