LNP-Delivered CAR-mRNA Enables in Vivo CAR-Macrophage Production for TYRP1-Targeted Therapy of Choroidal Melanoma

PURPOSE: To develop a macrophage-targeted therapy for choroidal melanoma using lipid nanoparticles (LNPs) that deliver TYRP1-CAR mRNA to reprogram tumor-associated macrophages. METHODS: intravitreal injection on days 3 and 6. Macrophage phenotype, CAR expression, and tumor progression were assessed using immunofluorescence, flow cytometry, and bioluminescence imaging. Safety was evaluated through blood biochemistry and histology. RESULTS: . The F4/80/MPLA-LNP-CAR mRNA treatment significantly reduced tumor burden (bioluminescence and tumor weight), increased M1 macrophage infiltration, and extended survival compared to controls. No systemic toxicity was observed in hematological, biochemical, or histological analyses. CONCLUSIONS: We demonstrate that macrophage-targeted MPLA-LNP delivery of TYRP1-CAR mRNA in a murine choroidal melanoma model reprograms tumor-associated macrophages toward an M1 phenotype, suppresses tumor growth, and prolongs survival through combined antigen-specific targeting and microenvironment remodeling.