A cancer vaccine factory based on autophagy and efferocytosis to enhance tumor immunotherapy

In situ cancer vaccines are a more promising immunotherapeutic strategy than traditional cancer vaccines. However, its clinical application is hindered by insufficient exposure and presentation of tumor-associated antigens (TAAs). Here, we report a co-delivery hydrogel (CCFA@Gel) based on autophagy and efferocytosis as a “cancer vaccine factory” to enhance tumor immunotherapy. CCFA@Gel is a temperature-sensitive hydrogel composed of fucoidan (Fuc)-coated chlorin e6 (Ce6)-chloroquine (CQ) self-assembly and apocynin (APO). After CCFA@Gel targeting tumor cells through the affinity of Fuc to P-selectin, Ce6 induces immunogenic cell death (ICD) by photodynamic therapy (PDT) to trigger the exposure of TAAs. CQ enhances the retention of TAAs by inhibiting autophagy, while APO enhances the presentation of TAAs by inhibiting the efferocytosis of tumor-associated macrophages (TAMs). In vivo results show that CCFA@Gel significantly inhibits primary tumors, as well as tumor metastasis and recurrence by enhancing the exposure, retention and presentation of TAAs. Our study provides a novel strategy for in situ vaccines development to enhance cancer immunotherapy.