Nanovaccines integrating endogenous antigens and pathogenic adjuvants elicit potent antitumor immunity

Abstract

Abstract Cancer nanovaccines have the ability to train the immune system to specifically recognize and eliminate tumor cells. However, the vaccine’s efficacy is hampered by limited access to draining lymph nodes, poor recognition and internalization by dendritic cells (DCs), as well as insufficient immunogenicity to elicit the DC maturation. To overcome these challenges, we developed potent vesicular cancer nanovaccines by fusing bacterial outer membrane vesicles (OMVs) and tumor cell membranes (TCMs), namely BTs. The bacteria-derived pathogenic adjuvants in BTs enabled DC targeting, promoted full maturation of DCs and antigen presentation by DCs. The TCMs in BTs assembled a multitude of diverse tumor endogenous antigens as training cues to generate multiantigenic antitumor immunity. Integrating the two components via a lipid bilayer assembly avoids the premature separation in the biological environment and enables the high spatial and temporal delivery of the antigens and adjuvants into the same DCs. Immunization with BTs containing as low as 1 μg of OMVs confers an excellent tumor prophylactic effect with ∼30 % of treated mice maintaining a tumor-free status for over 100 days. Moreover, the nanovaccines exhibit a remarkable therapeutic effect in treating established solid tumors and potentiate immune checkpoint blockade therapy. Overall, the BTs are promising as personalized cancer nanovaccines and carry no systemic side effects.