Synthetic SIGLEC9-based chimeric switch receptor augments the efficacy of CAR macrophages against glioblastoma - PubMed
7 hours ago
- #Glioblastoma
- #CAR-Macrophages
- #Immunotherapy
- CAR-M (Chimeric Antigen Receptor Macrophage) therapy shows promise for treating glioblastoma multiforme (GBM).
- The immunosuppressive tumor microenvironment (TME) limits the antitumorigenic phenotype of CAR-Ms, with Siglec-sialic acid signaling promoting a protumorigenic state.
- A synthetic SIGLEC9-based chimeric switch receptor (CSR) was developed to convert inhibitory signals into positive ones, enhancing CAR-M efficacy.
- Dual circRNAs delivered via macrophage-targeted ionizable lipid nanoparticles generate CSR-functionalized CAR-Ms in vitro and in vivo.
- Modified CAR-Ms maintain a proinflammatory state, exhibit superior phagocytic activity, and effectively eliminate IL13Rα2-positive tumor cells.
- An injectable nanoparticle-hydrogel system reprograms macrophages around the glioma resection cavity, triggering a locoregional antitumor immune response and long-term immunological memory.
- The engineered SIGLEC9-based CSR helps sustain an antitumoral CAR-M phenotype in the hypersialylated acidic TME, improving macrophage-based immunotherapy for GBM.