Zhang Jie, Fan Biao, Cao Guoliang, Huang Wenping, Jia Fuhao, Nie Guangjun, Wang Hai
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Adv Mater. 2022 Nov;34(47):e2205950. doi: 10.1002/adma.202205950. Epub 2022 Oct 18.
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.
基于树突状细胞（DCs）的疫苗是一种经批准的诱导有效抗原特异性免疫反应以消除肿瘤细胞的方法。然而，这种前景广阔的策略仍面临诸如肿瘤相关抗原（TAAs）负载、归巢至淋巴结、质量控制及其他限制等挑战。在此，开发了一种用于刺激TAAs特异性T细胞群体的个性化模拟DC纳米疫苗（nanoDC）。nanoDCs是利用具有树突状结构的纳米颗粒和来自成熟骨髓来源细胞（BMDCs）的膜制备而成。成熟的BMDCs受到由大肠杆菌和肿瘤细胞组装而成的纳米结构刺激，以有效递送TAAs，并通过干扰素基因刺激物（STING）途径诱导BMDCs成熟。通过维持共刺激标志物、I类分子（MHC-I）抗原复合物和淋巴细胞归巢受体，nanoDCs能有效迁移至淋巴结并产生有效的抗原特异性T细胞反应。因此，用nanoDCs进行疫苗接种可在体内强烈抑制肿瘤生长和转移形成。特别是，nanoDCs还能诱导记忆T细胞产生长期保护性免疫。本研究表明，nanoDCs可触发针对肿瘤的适应性免疫保护，用于个性化免疫治疗和精准医学。
