Converting primary tumor towards an in situ STING-activating vaccine via a biomimetic nanoplatform against recurrent and metastatic tumors

Abstract Currently, vaccine is a promising tumor prevention modality in cancer therapy. However, it is hard to elicit robust antitumor immunity in patients already afflicted with tumor, inspiring a need for a firenew and subversive cancer therapeutic vaccine. Herein, we reported an in situ STING (stimulator of interferon genes)-activating vaccination (ISSAV) strategy to completely convert primary tumor towards an in situ therapeutic STING vaccine for initiating highly effective and personalized antitumor immune responses. This ISSAV strategy represented a broad-spectrum cancer therapeutic vaccine, which break the shackles of heterogeneity and immunosuppression. We developed an ideational ingenious biomimetic nanoplatform (CMM-DiR) for achieving ISSAV strategy, which encapsulated STING-agonist (MnO2 NPs) and immobilized photothermal agent (DiR). In the tumor microenvironment (TME), CMM-DiR realized burst release of Mn2+, increased the pH value of TME, alleviated tumor hypoxia and induced the expose of numerous tumor-associated antigens from cancer cells. Accordingly, the primary tumor had the dual-function of as adequate antigens and STING agonist depots, thus transforming into a therapeutic STING vaccine. Importantly, the robust antitumor immunity of nanoplatform was observed in primary tumor, recurrent tumor, metastatic tumor and multinodular tumor, demonstrating that this ISSAV represents a technological advancement in the field of cancer vaccinations and personalized immunotherapy.