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 hematologi...

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Bibliographic Details
Published inBiomicrofluidics Vol. 18; no. 6; pp. 064105 - 64117
Main Authors Chen, Yu-Hsi, Mirza, Mahnoor, Jiang, Ruoyu, Lee, Abraham P.
Format Journal Article
LanguageEnglish
Published United States American Institute of Physics 01.12.2024
Subjects
Antigens
Cancer
Cytokines
Density
Dosage
Gene expression
Leukemia
Lymphocytes
Microfluidics
Receptors
Shearing
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Summary: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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ISSN:1932-1058
1932-1058
DOI:10.1063/5.0231595