Introduction

Tumor vaccine has been a research boom for cancer immunotherapy, while its therapeutic outcome is severely depressed by the vulnerable in vivo delivery efficiency. Moreover, tumor immune escape is also another intractable issue, which has badly whittled down the therapeutic efficiency.

Objectives

Our study aims to solve the above dilemmas by cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy.

Methods

The minimalist antigen and adjuvant co-delivery nanovaccine was developed by employing natural polycationic protamine (PRT) to carry the electronegative ovalbumin (OVA) antigen and unmethylated Cytosine-phosphorothioate-Guanine (CpG) adjuvant via convenient chemical bench-free “green” preparation without chemical-synthesis and no organic solvent was required, which could preserve the immunological activities of the antigens and adjuvants. On that basis, PD-1 antibody (aPD-1) was utilized to block the tumor immune escape and cooperate with the nanovaccine by maintaining the tumoricidal-activity of the vaccine-induced T cells.

Results

Benefited from the polycationic PRT, the facile PRT/CpG/OVA nanovaccine displayed satisfactory delivery performance, involving enhanced cellular uptake in dendritic cells (DCs), realizable endosomal escape and promoted stimulation for DCs’ maturation. These features would be helpful for the antitumor immunotherapeutic efficiency of the nanovaccine. Furthermore, the cooperation of the nanovaccine with aPD-1 synergistically improved the immunotherapy outcome, profiting by the cooperation of the “T cell induction” competency of the nanovaccine and the “T cell maintenance” function of the aPD-1.

Conclusion

This study will provide new concepts for the design and construction of facile nanovaccines, and contribute valuable scientific basis for cancer immunotherapy.

中文翻译：

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将极简纳米疫苗与 PD-1 阻断剂合作实现有效可行的癌症免疫治疗

介绍

肿瘤疫苗一直是癌症免疫疗法的研究热潮，而其治疗结果因体内传递效率脆弱而严重受压。此外，肿瘤免疫逃逸也是另一个棘手的问题，严重降低了治疗效率。

目标

我们的研究旨在通过将极简纳米疫苗与 PD-1 阻断剂相结合，实现有效可行的癌症免疫治疗，从而解决上述难题。

方法

通过使用天然聚阳离子鱼精蛋白 (PRT) 携带负电性卵清蛋白 (OVA) 抗原和未甲基化的胞嘧啶-硫代磷酸-鸟嘌呤 (CpG) 佐剂，通过方便的化学台式“绿色”制剂，开发了极简的抗原和佐剂共递送纳米疫苗。化学合成无需有机溶剂，可保持抗原和佐剂的免疫活性。在此基础上，利用PD-1抗体（aPD-1）阻断肿瘤免疫逃逸，并通过维持疫苗诱导的T细胞的杀肿瘤活性与纳米疫苗协同作用。

结果

受益于聚阳离子 PRT，简便的 PRT/CpG/OVA 纳米疫苗表现出令人满意的递送性能，包括增强的树突状细胞 (DC) 中的细胞摄取、可实现的内体逃逸和促进 DC 成熟的刺激。这些特征将有助于纳米疫苗的抗肿瘤免疫治疗效率。此外，纳米疫苗与aPD-1的合作协同改善了免疫治疗的效果，受益于纳米疫苗的“T细胞诱导”能力和aPD-1的“T细胞维持”功能的协同作用。

结论

该研究将为简便纳米疫苗的设计和构建提供新的理念，为癌症免疫治疗提供有价值的科学依据。