合作简约纳米疫苗与 PD-1 阻断联合进行有效可行的癌症免疫治疗。
Cooperating minimalist nanovaccine with PD-1 blockade for effective and feasible cancer immunotherapy.
机构信息
College of Pharmacy, Weifang Medical University, Weifang 261053, China.
Collaborative Innovation Center for Target Drug Delivery System, Weifang Medical University, Weifang 261053, China.
出版信息
J Adv Res. 2021 Aug 19;35:49-60. doi: 10.1016/j.jare.2021.08.011. eCollection 2022 Jan.
INTRODUCTION
Tumor vaccine has been a research boom for cancer immunotherapy, while its therapeutic outcome is severely depressed by the vulnerable 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.
简介
肿瘤疫苗作为癌症免疫疗法的研究热点,但其治疗效果受到脆弱的递送效率的严重抑制。此外,肿瘤免疫逃逸也是另一个棘手的问题,严重降低了治疗效果。
目的
本研究旨在通过合作最小化纳米疫苗与 PD-1 阻断来解决上述困境,以实现有效可行的癌症免疫治疗。
方法
通过采用天然阳离子鱼精蛋白(PRT),将带负电荷的卵清蛋白(OVA)抗原和未甲基化的胞嘧啶-磷酸硫代鸟嘌呤(CpG)佐剂通过便捷的化学无柜台“绿色”制备共同递送至纳米疫苗中,无需化学合成且无需有机溶剂,从而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 细胞的细胞毒性活性与纳米疫苗协同作用。
结果
得益于阳离子 PRT,简便的 PRT/CpG/OVA 纳米疫苗表现出令人满意的递药性能,包括增强树突状细胞(DCs)的细胞摄取、实现内涵体逃逸并促进 DCs 的成熟刺激。这些特征有助于提高纳米疫苗的抗肿瘤免疫治疗效果。此外,纳米疫苗与 aPD-1 的合作协同提高了免疫治疗效果,得益于纳米疫苗的“T 细胞诱导”能力和 aPD-1 的“T 细胞维持”功能的合作。
结论
本研究将为简便纳米疫苗的设计和构建提供新的概念,并为癌症免疫治疗提供有价值的科学依据。