Li Minghui, Qin Mengmeng, Song Ge, Deng Hailiang, Wang Dakuan, Wang Xueqing, Dai Wenbing, He Bing, Zhang Hua, Zhang Qiang
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Asian J Pharm Sci. 2021 Jan;16(1):97-109. doi: 10.1016/j.ajps.2020.06.006. Epub 2020 Jul 27.
Currently, the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention. Still, the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination. In this study, we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens. Briefly, endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered, both as delivery vehicles and adjuvants. Then, these nanocarriers are coated with lipids and B16-OVA tumor cell membranes, so the biomembrane proteins can serve as tumor-specific antigens. It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect, while membrane proteins including tumor associated antigen were transferred onto the nanocarriers. It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells, promote their maturation and antigen-presentation, facilitate lymph retention, and trigger obvious immune response. It was confirmed that the biomimetic vaccine could induce strong T-cell response, exhibit excellent tumor therapy and prophylactic effects, and simultaneously possess nice biocompatibility. In general, the present investigation might provide insights for the further design and application of antitumor vaccines.
目前,癌症免疫疗法取得了巨大进展,抗肿瘤疫苗备受关注。然而,佐剂和抗原的选择仍然是实现更好疫苗接种的最关键问题。在本研究中,我们基于生物相容性纳米载体和肿瘤细胞膜抗原提出了一种仿生抗肿瘤纳米疫苗。简而言之,设计并构建了具有潜在免疫增强作用的内源性焦磷酸钙纳米颗粒,其既作为递送载体又作为佐剂。然后,这些纳米载体用脂质和B16-OVA肿瘤细胞膜包被,因此生物膜蛋白可作为肿瘤特异性抗原。研究发现,焦磷酸钙纳米颗粒本身具有良好的相容性并具有佐剂作用,同时包括肿瘤相关抗原在内的膜蛋白被转移到纳米载体上。结果表明,这种仿生纳米疫苗可被树突状细胞很好地内吞,促进其成熟和抗原呈递,有利于淋巴滞留,并引发明显的免疫反应。证实该仿生疫苗可诱导强烈的T细胞反应,展现出优异的肿瘤治疗和预防效果,同时具有良好的生物相容性。总体而言,本研究可能为抗肿瘤疫苗的进一步设计和应用提供思路。