A Bioinspired Nanovaccine for Personalized Cancer Immunotherapy

Poly I:C (pIC) can act on endosomal and cytosolic pathogen recognition receptors to enhance T cell immunity. However, the poor cytosolic delivery of pIC and lack of facile methods for codelivery with antigens limit its efficacy. Inspired by the structure of a virus, we developed a <i>l</i>ipo<i>n</i>ano<i>g</i>el (LNG) consisting of a nanogel core and lipid shell to address these challenges. An LNG-based vaccine increases the endosomal membrane permeability in a nanogel core-dependent manner, thus enhancing cytosolic sensing of pIC. LNG induces 44.9-fold stronger CD8+ T cell responses than soluble pIC or Hiltonol adjuvanted vaccines and even induces stronger CD8+ T cell responses than state-of-the-art lipid nanoparticle adjuvanted vaccines. Remarkably, the LNG vaccine regresses 100% TC1 tumors and even regresses 60% aggressive B16F10 tumors upon combination with αPD-L1. Our study provides a safe and effective strategy for enhancing T cell immunity and may inspire new approaches for cancer immunotherapy.