A versatile self-adjuvanting macro-microporous ZIF-8@Mn MOF platform for efficient antigen capture and presentation...

Personalized in situ tumor vaccines (ISTVs) have emerged as a promising approach to activating potent T cell-mediated anticancer immunity through the induction of immunogenic cell death (ICD) and the subsequent release of tumor-associated antigens (TAAs). However, their efficacy is limited by non-specific ICD, inadequate TAAs cross-presentation, and the stubborn immunosuppressive tumor microenvironment (TME). Here, we develop a novel ISTV platform (SOM-ZIF-8@Mn/ARV) integrating a specific ICD inducer (ARV-825), and a multifunctional antigen catcher (SOM-ZIF-8@Mn) to boost antitumor immunity. ARV-825, as a protein targeted degradation chimera (PROTAC), selectively degrades bromodomain-containing protein4 (BRD4) to induce potent ICD, while the produced TAAs are effectively captured by SOM-ZIF-8@Mn to in situ generate a vaccination effect. Leveraging its unique hierarchical porous structure and rough surface, SOM-ZIF-8@Mn exhibits enhanced antigen capture efficiency, enabling the adsorption of both soluble TAAs and tumor cell fragments. Additionally, Mn²⁺ released from SOM-ZIF-8@Mn under TME conditions activates the STING pathway, promotes dendritic cell maturation and antigen cross-presentation, thereby activating CD8⁺ T cells for efficient tumor-specific immunity. Furthermore, the platform reprograms tumor-associated macrophages into pro-inflammatory M1 phenotypes, alleviating TME immunosuppression. This ISTV platform triggers robust antitumor immunity and achieves significant tumor growth inhibition when combined with αPD-1 blockade. The SOM-ZIF-8@Mn/ARV platform represents a powerful and effective advancement in improving the antitumor immune efficiency of ISTVs, offering a straightforward approach to the challenges faced in tumor immunotherapy.