Immune-remodeling mRNAs expressing IRF8 or NIK generate durable anti-tumor immunity in multiple cancer models

Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune remodeling mRNAs (IR-mRNAs) encoding NF-κB inducing kinase (NIK) or interferon regulatory factor 8 (IRF8).

These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines, and priming anti-tumor CD8+ T cells. IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models via both intratumoral and intravenous delivery. Co-administration of IR- and OVA-mRNA elicited ~10-fold increase of antigen-specific CD8⁺ T cell responses, sustained long-term memory, and effectively prevented tumor growth in vaccinated mice.