In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy

Because of tumor heterogeneity and the immuno-suppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA nanorocket initiates the satellite-rocket separation procedure in the acidic tumor microenvironment, the FeSHK@B launch vehicle can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA satellite to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

Automated summary

This paper reports on a separable cancer vaccine, FeSHK@B-ovalbumin (OVA), based on bioadhesive nanoparticles (BNPs), which targets multi-epitope antigens and exhibits effective cancer immunotherapy. The FeSHK@B-OVA nanorocket initiates satellite-rocket separation in the acidic tumor microenvironment, leading to intracellular oxidative stress amplification. The prolonged drug retention within the tumor tissue triggers immunogenic cell death and enables robust antigen-specific antitumor immunity.