文献：

The construction of a lymphoma cell-based, DC-targeted vaccine, and its application in lymphoma prevention and cure

文献链接：

作者：

Tianlin Zhou, Jinrong Peng, Ying Hao, Kun Shi, Kai Zhou, Yun Yang, Chengli Yang, Xinlong He, Xinmian Chen, Zhiyong Qian

相关产品：

DSPE-PEG-FITC（磷脂-聚乙二醇-荧光素）

DSPE-PEG-Mannose（磷脂-聚乙二醇-甘露糖）

原文摘要：

In recent years, Non-Hodgkin lymphoma (NHL) has been one of the most fast-growing malignant tumor diseases. NHL poses severe damages to physical health and a heavy burden to patients. Traditional therapies (chemotherapy or radiotherapy) bring some benefit to patients, but have severe adverse effects and do not prevent relapse. The relevance of emerging immunotherapy options (immune-checkpoint blockers or adoptive cellular methods) for NHL remains uncertain, and more intensive evaluations are needed. In this work, inspired by the idea of vaccination to promote an immune response to destroy tumors, we used a biomaterial-based strategy to improve a tumor cell-based vaccine and constructed a novel vaccine named Man-EG7/CH@CpG with antitumor properties. In this vaccine, natural tumor cells are used as a vector to load CpG-ODN, and following lethal irradiation, the formulations were decorated with mannose. The study of the characterization of the doubleimproved vaccine evidenced the enhanced ability of DCs targeting and improved immunocompetence, which displayed an antitumor function.

In the lymphoma prevention model, the Man-EG7/CH@CpG vaccine restrained tumor formation with high efficiency. Furthermore, unlike the non-improved vaccine, the double-improved vaccine elicited an enhanced antitumor effect in the lymphoma treatment model. Next, to improve the moderate therapeutic effect of the mono-treatment method, we incorporated a chemotherapeutic drug (doxorubicin, DOX) into the process of vaccination and devised a combination regimen. Fortunately, a tumor inhibition rate of ~85% was achieved via the combination therapy, which could not be achieved by mono-chemotherapy or mono-immunotherapy. In summary, the strategy presented here may provide a novel direction in the establishment of a tumor vaccine and is the basis for a prioritization scheme of immuno-chemotherapy in enhancing the therapeutic effect on NHL.

DSPE - PEG - Mannose（1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺 - 聚乙二醇 - 甘露糖）主要由三部分组成。DSPE 部分具有亲脂性，其包含两条长链的硬脂酸，这使得该分子能够与脂质环境相互作用，如嵌入脂质双层结构。PEG（聚乙二醇）在这里起到连接和改善性质的作用，它增加了分子整体的亲水性，同时可以减少在体内的非特异性蛋白吸附，有助于延长在血液循环中的时间。Mannose（甘露糖）是一种糖类，它是这个分子的活性部分，能够与细胞表面的甘露糖受体相互作用。基于此，该文献制备了Man-EG7/CH@CpG，流程如下：

图：作用机制

将CpG-ODN分别与壳聚糖以不同质量比混合。然后在琼脂糖凝胶上进行电泳，用Gelred染色。使用化学博士成像仪对凝胶进行可视化和成像。转染前24小时，将EG7-OVA细胞接种到6孔板中。CY5标记的CpG-ODN（作为可视化报告基因，以检测摄取效率。将壳聚糖和CpG-ODN在RPMI-1640培养基（无血清）中常温培养，然后洒入培养的tumour细胞中。以DOTAP/CpG或Lipo3K/CpG复合物和等量的CpG-ODN作为对照。每孔均在显微镜下拍摄照片，后用流式细胞术检测转染效率。EG7/壳聚糖/CpG复合物在致命辐照条件下使用RS-2000辐照设备被灭活。然后，将DSPE-PEG-Mannose与灭活的修饰tumour细胞混合，用佐剂吸收。该制备的配方被标记为Man-EG7/CH@CpG。

图：合成流程

结论：

该文献通过精细的化学合成技术与先进的生物医学研究方法，成功制备出了基于DSPE-PEG-Mannose（一种具有特定糖基修饰的磷脂-聚乙二醇共聚物）合成的Man-EG7/CH@CpG纳米载体。对这一双改进型疫苗的特性进行深入的研究后，结果表明，增强了树突状细胞（作为免疫系统中的重要抗原呈递细胞）的靶向能力，能够更准确地作用于目标细胞，从而提高了整体的免疫应答水平。