Yang Xiqin, Yu Tong, Zeng Yingping, Lian Keke, Zhou Xueqing, Ke Jia, Li Yinghong, Yuan Hong, Hu Fuqiang
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Zhejiang Institute for Food and Drug Control, Hangzhou 310052, China.
Biomacromolecules. 2020 Jul 13;21(7):2818-2828. doi: 10.1021/acs.biomac.0c00518. Epub 2020 Jun 16.
Lymph nodes are proposed as the intriguing target in cancer immunotherapy, and cellular immunity is vital for vaccines to fight against cancer. However, inefficient delivery of vaccines to lymph nodes and deficient lysosomal escape of antigens result in weak cellular immunity, which restrains the strength of vaccines in inducing antitumor immune responses. Hence, dendritic cell membrane (DCM)/histidine-modified stearic acid-grafted chitosan (HCtSA)/ovalbumin (OVA) micelles, as pH-responsive biomimetic vaccines, were fabricated to target lymph nodes and induce cellular immunity for enhanced antitumor immune responses. DCM/HCtSA/OVA micelles exhibited pH-dependent antigen release behavior, which resulted in efficient escape of antigens from dendritic cell (DC) lysosomes. Besides, DCM/HCtSA/OVA micelles accumulated and reserved in the lymph nodes, which ensured effective uptake by DCs. Importantly, DCM/HCtSA/OVA micelles induced potent T cell immune responses, promoted secretion of antitumor-related cytokines, and notably inhibited tumor growth. Overall, DCM/HCtSA/OVA micelles exhibit great potential in targeted immunotherapy and can provide guidance for the design of vaccines.
淋巴结被认为是癌症免疫治疗中引人关注的靶点,细胞免疫对于疫苗对抗癌症至关重要。然而,疫苗向淋巴结的递送效率低下以及抗原的溶酶体逃逸不足导致细胞免疫较弱,这限制了疫苗诱导抗肿瘤免疫反应的强度。因此,制备了树突状细胞膜(DCM)/组氨酸修饰的硬脂酸接枝壳聚糖(HCtSA)/卵清蛋白(OVA)胶束作为pH响应性仿生疫苗,以靶向淋巴结并诱导细胞免疫,增强抗肿瘤免疫反应。DCM/HCtSA/OVA胶束表现出pH依赖性抗原释放行为,这导致抗原从树突状细胞(DC)溶酶体中有效逃逸。此外,DCM/HCtSA/OVA胶束在淋巴结中积累并保留,这确保了DCs的有效摄取。重要的是,DCM/HCtSA/OVA胶束诱导了强烈的T细胞免疫反应,促进了抗肿瘤相关细胞因子的分泌,并显著抑制了肿瘤生长。总体而言,DCM/HCtSA/OVA胶束在靶向免疫治疗中具有巨大潜力,并可为疫苗设计提供指导。
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