Antigen Self-Presented Personalized Nanovaccines Boost the Immunotherapy of Highly Invasive and Metastatic Tumors

Dendritic cell (DC)-based vaccines have shown promise in adoptive cell therapy for enhancing the antigen-specific response of antitumor immunity. However, their clinical efficacy is limited by the less-presented tumor-associated antigens (TAAs) through MHC I and low lymph node homing efficiency. Herein, to address these issues, we rationally design and fabricate DC-based nanovaccines by coating Cu2–x Se nanoparticles (CS NPs) with the membrane of matured DCs (named as DCNV­(CSD) nanovaccines). We reveal the important roles of CS NPs in the DCNV­(CSD) nanovaccines from three aspects: (1) inducing the immunogenic cell death of tumor cells to expose abundant TAAs; (2) promoting the escape of TAAs from the lysosomes of DCs during the antigen presenting process through MHC I; (3) sustainably releasing traces of copper ions to promote the proliferation of T cells. Our DCNV­(CSD) nanovaccines are characterized with high expressions of MHC I, CD80, CD86, CCR7, and ICAM-1 proteins, which not only endow them with abundantly processed specific TAAs, but also a strong capability of homing to the lymph nodes. The homing capability of our small DCNV­(CSD) nanovaccines is better than that of matured DCs. More importantly, they can elicit the strong response of potent antispecific CD8+ T cells for antitumor immunotherapy, as tested in the treatment of highly invasive glioblastoma and highly metastatic melanoma. Additionally, DCNV­(CSD) nanovaccines can generate memory T cells (TEM) in the spleen of mice to effectively prevent the recurrence of treated tumors. This work demonstrates a universal approach to fabricate high-performance DC-based nanovaccines for tumor immunotherapy by using versatile CS NPs.