Yu-Hsi Chen, Mahnoor Mirza, Ruoyu Jiang, Abraham P Lee
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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.
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...