Lipid nanoparticles that co-deliver poly(I:C) and short peptide antigens elicit anti-tumor responses with vaccination

Polyriboinosinic–polyribocytidylic acid (pIC) is a Toll-like receptor 3 (TLR3) agonist that has been used as a vaccine adjuvant. Here, we show that an integrated lipid nanoparticle (LNP) which co-delivers pIC together with short peptide immunogens potentiates therapeutic cancer vaccination. Ionizable lipids encapsulated pIC in the core of lipid nanoparticles via electrostatic interaction, while co-inclusion of cobalt porphyrin-phospholipid (CoPoP) allowed for display of short peptides modified with 3 histidine residues on the particle surface. Co-delivery of pIC and antigens within the same particle potently elicited antigen-specific CD8⁺T cell responses, leading to effective therapeutic anti-tumor effects in both Renca and TC-1 murine tumor models. Unexpectedly, the inclusion of CoPoP in the LNP appeared to mitigate cytotoxicity induced by pIC in LNP formulations and treatments were tolerated in mice based on serum chemistry and cytokine levels.