Liu Liping, Zhao Jiayu, Huang Zichao, Xu Yudi, Chen Hongyu, Qiao Ruirui, Song Wantong, Tang Zhaohui, Davis Thomas P, Chen Xuesi
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
University of Science and Technology of China, Hefei 230026, China.
Fundam Res. 2023 May 11;5(1):183-191. doi: 10.1016/j.fmre.2023.03.018. eCollection 2025 Jan.
In recent years, the use of nanotechnologies to improve immunotherapy efficiency has attracted increasing interest in preventive and therapeutic cancer vaccine design. However, current nanocarriers are restricted by difficulties in the systematic spatial coordinative transport of antigens, which greatly hampers the immune response efficacy of nanovaccines. Herein, we designed a mannan-decorated stimulator of the interferon genes (STING)-activating vaccine carrier for spatial coordinative stimulation of antigen-specific immune responses and elicitation of robust antitumor immunity. Mannan-decoration as the shell could significantly enhance the lymph node draining ability of the nanovaccines, especially in CD8 dendritic cells (DCs). Azole molecule end-capped polylactic acid-polyethylenimine (PLA-PEI-4BImi) with innate stimulating activity was applied as the inner core for coordinating antigen-presenting cell activation and antigen cross-presentation. In the in vivo therapy study, single usage of this nanovaccine could achieve a 93% tumor suppression rate in the B16-OVA tumor model, which is superior to the commercialized aluminum adjuvant. This study demonstrates that a rational design of vaccine carriers for solving spatial transmission issues could greatly improve cancer vaccine efficiencies.
近年来，利用纳米技术提高免疫治疗效率在预防性和治疗性癌症疫苗设计方面引起了越来越多的关注。然而，当前的纳米载体受到抗原系统性空间协同运输困难的限制，这极大地阻碍了纳米疫苗的免疫反应效果。在此，我们设计了一种甘露聚糖修饰的干扰素基因刺激因子（STING）激活疫苗载体，用于空间协同刺激抗原特异性免疫反应并引发强大的抗肿瘤免疫力。作为外壳的甘露聚糖修饰可显著增强纳米疫苗的淋巴结引流能力，尤其是在CD8树突状细胞（DCs）中。具有固有刺激活性的唑分子封端聚乳酸-聚乙烯亚胺（PLA-PEI-4BImi）被用作内核，以协同抗原呈递细胞激活和抗原交叉呈递。在体内治疗研究中，单次使用这种纳米疫苗在B16-OVA肿瘤模型中可实现93%的肿瘤抑制率，优于商业化的铝佐剂。这项研究表明，合理设计用于解决空间传递问题的疫苗载体可大大提高癌症疫苗效率。
