基于微流体的剂量控制细胞内mRNA递送平台在CAR - T细胞上滴定嵌合抗原受体。

IF 2.6 4区 工程技术 Q2 BIOCHEMICAL RESEARCH METHODS Biomicrofluidics Pub Date : 2024-12-18 eCollection Date: 2024-12-01 DOI:10.1063/5.0231595
Yu-Hsi Chen, Mahnoor Mirza, Ruoyu Jiang, Abraham P Lee
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引用次数: 0

摘要

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,特别是在治疗各种血癌患者,尤其是b细胞急性淋巴细胞白血病方面。近年来,CAR - t细胞疗法已被研究用于治疗其他血液系统恶性肿瘤和实体肿瘤。尽管CAR -t细胞疗法取得了显著的成功,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细胞表面密度来减少与CRS相关的促炎细胞因子释放。我们发现CAR表达密度可以通过声电微流控平台在原代T细胞表面进行滴定。该平台通过均匀混合和剪切细胞进行剂量控制递送,将大约相同数量的CAR基因编码mRNA递送到每个T细胞中。
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Titrating chimeric antigen receptors on CAR T cells enabled by a microfluidic-based dosage-controlled intracellular mRNA delivery platform.

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.

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来源期刊
Biomicrofluidics
Biomicrofluidics 生物-纳米科技
CiteScore
5.80
自引率
3.10%
发文量
68
审稿时长
1.3 months
期刊介绍: Biomicrofluidics (BMF) is an online-only journal published by AIP Publishing to rapidly disseminate research in fundamental physicochemical mechanisms associated with microfluidic and nanofluidic phenomena. BMF also publishes research in unique microfluidic and nanofluidic techniques for diagnostic, medical, biological, pharmaceutical, environmental, and chemical applications. BMF offers quick publication, multimedia capability, and worldwide circulation among academic, national, and industrial laboratories. With a primary focus on high-quality original research articles, BMF also organizes special sections that help explain and define specific challenges unique to the interdisciplinary field of biomicrofluidics. Microfluidic and nanofluidic actuation (electrokinetics, acoustofluidics, optofluidics, capillary) Liquid Biopsy (microRNA profiling, circulating tumor cell isolation, exosome isolation, circulating tumor DNA quantification) Cell sorting, manipulation, and transfection (di/electrophoresis, magnetic beads, optical traps, electroporation) Molecular Separation and Concentration (isotachophoresis, concentration polarization, di/electrophoresis, magnetic beads, nanoparticles) Cell culture and analysis(single cell assays, stimuli response, stem cell transfection) Genomic and proteomic analysis (rapid gene sequencing, DNA/protein/carbohydrate arrays) Biosensors (immuno-assay, nucleic acid fluorescent assay, colorimetric assay, enzyme amplification, plasmonic and Raman nano-reporter, molecular beacon, FRET, aptamer, nanopore, optical fibers) Biophysical transport and characterization (DNA, single protein, ion channel and membrane dynamics, cell motility and communication mechanisms, electrophysiology, patch clamping). Etc...
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