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A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
Advances in ex vivo mRNA-based gene transfer for cell-based cancer immunotherapy
Florian Van Oers1,2, Zoi Katana1, Donovan Flumens1
1Tumor Immunology Group, Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Antwerp, Belgium.
Abstract:
Electroporation of messenger RNA (mRNA) is an ex vivo non-integrating gene transfer technique used in immune-cell-based trials for cancer to transiently supply immune cells with multiple proteins. This technique has been used to engineer dendritic cells and B cells with tumor-associated antigens to boost the immune system of cancer patients and to redirect the anti-tumor activity of T cells and natural killer cells with immune receptors. Although gene delivery via mRNA electroporation results only in transient expression of the protein of interest, many investigators and clinicians consider it as a feasible, flexible, and safe technique, compared with stable expression methods using viral vectors. In this review, we discuss the efficacy of mRNA electroporation for gene transfer and assess the strengths and limitations of this technique for redirecting and boosting immune responses against various tumor antigens in cancer immunotherapy.
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