Abstract
We report on the utility of a "super-adjuvant" nanoparticle (NP) system as a modular, customizable platform for next-generation cancer vaccination. Using nanomaterials engineering technology, we aim to harness not only the effective adjuvanticity of whole-pathogen vaccines, but also the safety of subunit vaccines. Our lipid-based NP platform co-encapsulates agonists of the stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) pathways to promote synergistic production of type I interferons and other proinflammatory cytokines in innate antigen-presenting dendritic cells and macrophages. Compared to empty NPs and free agonists, dual-adjuvant NPs administered with antigenic peptides or tumor cell lysate promote increased antigen processing and presentation, drain efficiently to nearby lymph nodes, increase polyfunctional tumor-specific T and B cells, and improve tumor-free outcomes upon vaccination and subsequent challenge with multiple aggressive tumor cells.