MAGNETIC BEAD-SENSITIZED OPTOPORATION COUPLED WITH ANTIBODIES-BASED ACTIVATION FOR MRNA CAR-T CELL MANUFACTURING

Magnetic bead-sensitized optoporation coupled with antibodies-based activation for mRNA CAR-T cell manufacturing

Magnetic bead-sensitized optoporation coupled with antibodies-based activation for mRNA CAR-T cell manufacturing

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Immunotherapy is facing a revolution with the advent of immune cell engineering.Chimeric antigen receptor (CAR)-T cell therapy has shown unprecedented efficacy in B cell malignancies and is now being evaluated in other disease areas.Viral transduction is the most Raypak ELS 3-Series Heater Parts common method for immune cell genetic engineering, but presents important limitations, such as high reagent costs and regulatory concerns due to mutagenesis risk.One prevailing non-viral gene delivery strategy relies on the electroporation of non-integrating RNA.However, most modern electroporation technologies also require high reagent costs and rely on the use of proprietary software and transfection buffers.

Nanoparticle-sensitized optoporation represents an alternative method for transient permeabilization of cells.Here, we introduce magnetic bead-sensitized optoporation, in which commercially available superparamagnetic beads coupled with anti-human CD3 and CD28 antibodies are used as photosensitizers for efficient genetic cargo delivery into human primary T cells and other immune cells.We show that magnetic bead-sensitized optoporation Canteen of human T cells generates functional mRNA-based CAR-T cells without affecting T cell product memory phenotype or activation potential.Importantly, optoporated T cells exhibited a greater proliferation capacity relative to electroporated T cells.In conclusion, our findings suggest that magnetic bead-sensitized optoporation holds promise as mRNA delivery strategy for immune cell therapy.

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