Direct Presentation of Tumor‐Associated Antigens to Induce Adaptive Immunity by Personalized Dendritic Cell‐Mimicking Nanovaccines

Dendritic cells (DCs)‐based vaccines are an approved method for inducing potent antigen‐specific immune responses to eliminate tumor cells. However, this promising strategy still faces challenges such as tumor‐associated antigens (TAAs) loading, lymph node homing, quality control, and other limitations. Here, a personalized DC‐mimicking nanovaccine (nanoDC) for stimulation of TAAs‐specific T cell populations is developed. The nanoDCs are fabricated using nanoparticles with dendritic structure and membranes from mature bone‐marrow‐derived cells (BMDCs). Mature BMDCs are stimulated by nanostructures assembled from Escherichia coli and tumor cells to efficiently deliver TAAs and induce BMDCs maturation through the stimulator of interferon genes (STING) pathway. By maintaining co‐stimulatory markers, molecules class I (MHC‐I) antigen complexes and lymphocyte homing receptors, nanoDCs efficiently migrate to lymph nodes and generate potent antigen‐specific T cell responses. Consequently, vaccination with nanoDCs strongly inhibits the tumor growth and metastases formation in vivo. In particular, nanoDCs can also induce memory T cells for long‐term protective immunity. This study demonstrates that nanoDCs can trigger adaptive immune protection against tumors for personalized immunotherapy and precision medicine. A personalized dendritic cells (DCs)‐mimicking nanovaccine (nanoDC) is reported to initiate tumor antigen‐specific cytotoxic T cells in lymph nodes. The nanoDCs inherit the advantages of DCs vaccines and overcome potential shortcomings of live cell‐based therapy, such as insufficient immunogenicity and insufficient lymph node delivery. As a proof‐of‐concept, nanoDCs vaccination effectively inhibits B16‐OVA and CT26 tumor growth and metastasis formation.