An in situ generated CAR-M with IFN-γ and negative dominance Sirpα isoform augments hepatocellular carcinoma immunotherapy - PubMed
5 hours ago
- #CD47-SIRPα blockade
- #HCC immunotherapy
- #CAR-M
- Developed a novel CAR-M targeting GPC3 for HCC, incorporating IFN-γ and SIRPαECD to enhance persistence and block CD47-SIRPα checkpoint.
- Used LNP-mRNA delivery for in situ generation; IFN-γ promoted M1 polarization via STAT1, while SIRPαECD competitively inhibited CD47 interaction.
- CAR-M showed improved pro-inflammatory activity, reprogrammed tumor microenvironment in murine HCC model, and phagocytosed human HCC organoids with tissue specificity.