免疫系统
抗原
癌症免疫疗法
细胞毒性T细胞
内化
抗原提呈细胞
抗原呈递
化学
树突状细胞
T细胞
免疫疗法
癌症研究
细胞生物学
免疫学
生物
细胞
体外
生物化学
作者
Yunting Zhang,Min Jiang,Guangsheng Du,Xiaofang Zhong,Chun-Ting He,Ming Qin,Yingying Hou,Rong Liu,Xun Sun
标识
DOI:10.1016/j.apsb.2022.03.017
摘要
The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.
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