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

作者：Tingting Wang, Mengxiao Han, Yaobao Han, Zhilin Jiang, Qing Yin Zheng, Hao Zhang, Zhen Li · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.3c11189 · 被引用次数：36 · 研究领域：Immunotherapy and Immune Responses、RNA Interference and Gene Delivery、Nanoplatforms for cancer theranostics

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 Cu 2– 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 (T EM ) in the sp...