Fluorinated lipid nanoparticles enable in vivo CAR-macrophage therapy in solid tumor and enhance anti PD-L1 immunotherapy - PubMed
7 hours ago
- #CAR-macrophages
- #Cancer immunotherapy
- #Fluorinated lipids
- Fluorinated lipid nanoparticles (LNPs) enable in vivo CAR-macrophage (CAR-M) therapy for solid tumors.
- CAR-M therapy leverages macrophages' tumor-homing, phagocytic ability, and tumor microenvironment remodeling with low cytokine release risk.
- A1F5C5, a fluorinated ionizable lipid, was identified as the top candidate for efficient mRNA delivery to macrophages.
- Fluorination enhances cellular uptake and endosomal dissociation, with five fluorine atoms optimizing membrane fusion for endosomal escape.
- F5-LNPs with hPSMA-targeted CAR mRNA reprogrammed the tumor microenvironment, reducing M2-like macrophages and boosting CD8+ T cell activity.
- Combining F5-CAR with anti-PD-L1 blockade achieved 100% complete tumor regression in MC38-hPSMA tumor-bearing mice.
- Fluorinated LNPs offer a scalable platform for in vivo CAR-M engineering against solid tumors.