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Recombinant baculovirus expressing the FrC-OVA protein induces protective antitumor immunity in an EG7-OVA mouse model.
Journal of Biological Engineering ( IF 5.6 ) Pub Date : 2019-10-22 , DOI: 10.1186/s13036-019-0207-y
Keigo Kondou 1 , Tomoyuki Suzuki 1 , Myint Oo Chang 1 , Hiroshi Takaku 1
Affiliation  

Background The baculovirus (BV) Autographa californica multiple nuclear polyhedrosis virus has been used in numerous protein expression systems because of its ability to infect insect cells and serves as a useful vaccination vector with several benefits, such as its low clinical risks and posttranslational modification ability. We recently reported that dendritic cells (DCs) infected with BV stimulated antitumor immunity. The recombinant BV (rBV) also strongly stimulated peptide-specific T-cells and antitumor immunity. In this study, the stimulation of an immune response against EG7-OVA tumors in mice by a recombinant baculovirus-based combination vaccine expressing fragment C-ovalbumin (FrC-OVA-BV; rBV) was evaluated. Results We constructed an rBV expressing fragment C (FrC) of tetanus toxin containing a promiscuous MHC II-binding sequence and a p30-ovalbumin (OVA) peptide that functions in the MHC I pathway. The results showed that rBV activated the CD8+ T-cell-mediated response much more efficiently than the wild-type BV (wtBV). Experiments with EG7-OVA tumor mouse models showed that rBV significantly decreased tumor volume and increased survival compared with those in the wild-type BV or FrC-OVA DNA vaccine groups. In addition, a significant antitumor effect of classic prophylactic or therapeutic vaccinations was observed for rBV against EG7-OVA-induced tumors compared with that in the controls. Conclusion Our findings showed that FrC-OVA-BV (rBV) induced antitumor immunity, paving the way for its use in BV immunotherapy against malignancies.

中文翻译:

表达 FrC-OVA 蛋白的重组杆状病毒在 EG7-OVA 小鼠模型中诱导保护性抗肿瘤免疫。

背景杆状病毒 (BV) Autographa californica 多核多角体病毒已被用于多种蛋白质表达系统,因为它能够感染昆虫细胞,并作为一种有用的疫苗接种载体,具有多种益处,例如其低临床风险和翻译后修饰能力。我们最近报道了感染 BV 的树突状细胞 (DC) 刺激了抗肿瘤免疫。重组 BV (rBV) 还强烈刺激肽特异性 T 细胞和抗肿瘤免疫。在这项研究中,评估了表达片段 C-卵白蛋白 (FrC-OVA-BV; rBV) 的基于重组杆状病毒的组合疫苗对小鼠 EG7-OVA 肿瘤免疫反应的刺激作用。结果 我们构建了一个表达破伤风毒素片段 C (FrC) 的 rBV,该片段包含一个混杂的 MHC II 结合序列和一个在 MHC I 途径中起作用的 p30-卵清蛋白 (OVA) 肽。结果表明,rBV 比野生型 BV (wtBV) 更有效地激活了 CD8+ T 细胞介导的反应。EG7-OVA 肿瘤小鼠模型的实验表明,与野生型 BV 或 FrC-OVA DNA 疫苗组相比,rBV 显着降低了肿瘤体积并增加了存活率。此外,与对照组相比,对于 rBV 对 EG7-OVA 诱导的肿瘤,观察到经典预防性或治疗性疫苗接种的显着抗肿瘤作用。结论 我们的研究结果表明,FrC-OVA-BV (rBV) 可诱导抗肿瘤免疫,为其在 BV 免疫治疗恶性肿瘤中的应用铺平了道路。
更新日期:2020-04-22
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