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Lipid-based mRNA chimeric antigen receptor T cells for enhanced in vitro antitumor activity

ABSTRACT: Chimeric antigen receptor (CAR) T cell therapy provides substantial clinical benefits in hematologic malignancies. However, cell engineering using conventional viral vectors is costly, labor-intensive, and prone to safety risks, while electroporation-induced cellular damage limits manufacturing scalability. This study reports a safe, high-efficiency, nonviral platform for generating mRNA-engineered CAR-T cells. Herein, eight ionizable lipids are synthesized and formulated into lipid nanoparticles. Systematic screening and structural optimization identified Lipid 6 as the lead candidate. Transfection efficiency is validated by delivering eGFP mRNA into DC2.4, peripheral blood mononuclear, dendritic, and natural killer cells. Murine models confirm robust in vivo expression and a favorable safety profile. Lipid 6–mediated delivery of MUC1 mRNA generates MUC1–CAR-T cells characterized by high surface receptor expression and potent cytotoxicity against MUC1-positive tumor cells. These findings establish Lipid 6 as a feasible strategy for primary human T-cell engineering, facilitating functional CAR expression with minimal toxicity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE338028 | GEO | 2026/08/12

REPOSITORIES: GEO

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