Super-adjuvant nanoparticles for platform cancer vaccination.

Kane, Griffin I; Naylor, Tiana E; Lusi, Ellis F; Brassil, Meghan L; Wigglesworth, Kim; Dinnell, Ronnie W; Diaz-Infante, Miranda B; Whiteman, Leah M et al. · Cell Rep Med · 2025

basic_science · Level V

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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.

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