DNA carried by fat-based particles triggers cancer-fighting immune cells and improves anti-PD-L1 treatment

DNA-LNP treatment triggered strong cytokine induction and robust CD8+ T cell recruitment to the tumor microenvironment.

• Immune checkpoint inhibitors (ICIs) may improve cancer treatment but are effective only for a subset of patients due to limited preexisting antitumor immunity.
• Intracellular delivery of noncoding dsDNA in lipid nanoparticles is associated with activation of immune pathways that enhance antitumor responses.
• In multiple animal models, DNA-LNP treatment resulted in potent CD8+ T cell-dependent antitumor effects and increased survival.
• Empty lipid nanoparticles did not induce significant cytokine elevation or antitumor effects, indicating that specific pathways were activated by the DNA-LNPs.
• DNA-LNPs showed a synergistic effect with anti-PD-L1, significantly prolonging survival in both ICI-responsive and ICI-resistant tumor models.

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