Journal
ADVANCED MATERIALS
Volume 34, Issue 47, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202205950
Keywords
antigen presentation; cancer immunotherapy; dendritic cell; personalized vaccine
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Funding
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB36000000]
- National Natural Science Foundation of China [31971307]
- Start-up Foundation of National Center for Nanoscience and Technology
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This study developed a personalized DC-mimicking nanovaccine for stimulating TAAs-specific T cell populations. By inducing BMDCs maturation and delivering TAAs through nanostructures, the nanoDCs efficiently generated potent antigen-specific T cell responses, leading to inhibition of tumor growth and metastases formation.
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.
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