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.

当前，疫苗是癌症治疗中有希望的肿瘤预防手段。然而，很难在已经患有肿瘤的患者中获得强大的抗肿瘤免疫力，从而激发了对新型和颠覆性癌症治疗疫苗的需求。本文中，我们报道了原位STING（干扰素基因的刺激物）激活疫苗接种（ISSAV）策略，可将原发肿瘤完全转化为原位治疗性STING疫苗，以启动高效和个性化的抗肿瘤免疫应答。这种ISSAV策略代表了一种广谱的癌症治疗疫苗，它打破了异质性和免疫抑制的束缚。我们开发了一种构思巧妙的仿生纳米平台（CMM-DiR）以实现ISSAV策略，该策略封装了STING激动剂（MnO ₂NPs）和固定化的光热剂（DiR）。在肿瘤微环境（TME）中，CMM-DiR实现了Mn ^2+的爆发释放，增加了TME的pH值，减轻了肿瘤的缺氧，并诱导了癌细胞中多种肿瘤相关抗原的暴露。因此，原发性肿瘤具有作为适当抗原和STING激动剂贮库的双重功能，从而转化为治疗性STING疫苗。重要的是，在原发性肿瘤，复发性肿瘤，转移性肿瘤和多结节性肿瘤中观察到了纳米平台强大的抗肿瘤免疫力，表明该ISSAV代表了癌症疫苗接种和个性化免疫治疗领域的技术进步。