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A novel rapid modularized hepatitis B core virus-like particle-based platform for personalized cancer vaccine preparation via fixed-point coupling.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2020-05-16 , DOI: 10.1016/j.nano.2020.102223
Mei Ji 1 , Jie Zhu 2 , Xi-Xiu Xie 3 , Dong-Qun Liu 1 , Bin Wang 3 , Zhuo Yu 4 , Rui-Tian Liu 3
Affiliation  

Personalized cancer vaccine which targets neoepitopes shows great promise for cancer treatment. However, rapid preparation is a critical challenge for clinical application of personalized cancer vaccine. Genetic recombination and chemical modification are a time-consuming “trial and error” pattern for making vaccines. Here we first constructed a platform for peptide vaccine preparation by inserting SpyCatcher into the major immunodominant region (MIR) of hepatitis B core protein (HBc) (1-183). The resulted recombinant protein HBc(1-183)-SpyCatcher (HBc(1-183)-S) assembled to virus-like particles (VLPs) and readily bound to SpyTag conjugated with OVA epitope peptides by just mixing, forming HBc(1-183)-S-OVA. HBc(1-183)-S-OVA VLPs effectively induced dendritic cell maturation. Our further results indicated that HBc(1-183)-S-OVA VLPs vaccination inhibited tumor growth in both prophylactic and treatment ways in E.G7-OVA tumor bearing mice by generating significant OVA-specific cytotoxic T lymphocyte responses. Our study provides a simple, rapid, efficient and universal HBc-based platform for the preparation of personalized cancer vaccine.



中文翻译:

一种新型的快速模块化的基于乙肝核心病毒样颗粒的平台,用于通过定点偶联制备个性化癌症疫苗。

针对新表位的个性化癌症疫苗显示出对癌症治疗的巨大希望。然而,快速制备对于个性化癌症疫苗的临床应用是关键的挑战。遗传重组和化学修饰是制备疫苗的费时的“反复试验”模式。在这里,我们首先通过将SpyCatcher插入乙型肝炎核心蛋白(HBc)的主要免疫优势区(MIR)(1-183)中,构建了肽疫苗制备平台。所得重组蛋白HBc 1-183 -SpyCatcher(HBc 1-183 -S)组装成病毒样颗粒(VLP),并通过混合而易于结合至与OVA表位肽缀合的SpyTag,形成HBc (1- 183) -S-OVA。的HBc (1-183)-S-OVA VLP有效诱导树突状细胞成熟。我们的进一步结果表明,HBc (1-183) -S-OVA VLP疫苗接种通过产生明显的OVA特异性细胞毒性T淋巴细胞应答,在预防和治疗E.G7-OVA荷瘤小鼠中抑制了肿瘤的生长。我们的研究为制备个性化癌症疫苗提供了一个简单,快速,高效且通用的基于HBc的平台。

更新日期:2020-05-16
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