Hybrid LNP Prime Dendritic Cells for Nucleotide Delivery

Abstract The efficient activation of professional antigen‐presenting cells—such as dendritic cells (DC)—in tumors and lymph nodes is critical for the design of next‐generation cancer vaccines and may be able to provide anti‐tumor effects by itself through immune stimulation. The challenge is to stimulate these cells without causing excessive toxicity. It is hypothesized that a multi‐pronged combinatorial approach to DC stimulation would allow dose reductions of innate immune receptor‐stimulating TLR3 agonists while enhancing drug efficacy. Here, a hybrid lipid nanoparticle (LNP) platform is developed and tested for double‐stranded RNA (polyinosinic:polycytidylic acid for TLR3 agonism) and immune modulator (L‐CANDI) delivery. This study shows that the ≈120 nm hybrid nanoparticles‐in‐nanoparticles effectively eradicate tumors by themselves and generate long‐lasting, durable anti‐tumor immunity in mouse models.