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

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. An in situ STING-activating vaccination (ISSAV) strategy is designed to convert primary tumor towards in situ therapeutic STING vaccine with entire spectrum of tumor-associated antigens and adequate STING agonist. ISSAV strategy initiates personalized tumor immunotherapy for modulating the systemic immune response to promote the incredible therapeutic efficacy on different types and stages of insufficient immunogenic tumors. [Display omitted] •An in situ STING-activating vaccination (ISSAV) strategy was developed for combating incurable tumors.•ISSAV strategy can completely convert primary tumor towards therapeutic STING vaccine.•ISSAV strategy initiated highly effective and personalized antitumor immune responses.•ISSAV strategy also created a favorable tumor microenvironment for T lymphocyte infiltration.