重组病毒蛋白纳米颗粒治疗肺腺癌作用  

Therapeutic efficacy of recombinant virus protein nanoparticle for pulmonary adenocarcinoma in subcutaneous tumor mice model

作　　者：周文亭[1] 邹烨宁 沈立萍[1] 毕胜利[1] Zhou Wenting;Zou Yening;Shen Liping;Bi Shengli(NHC Key Laboratory of Medical Virology and Viral Diseases,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China;College of Life Science and Technology,Beijing University of Chemical Technology,Beijing 100029,China)

机构地区：[1]中国疾病预防控制中心病毒病预防控制所、国家卫生健康委员会医学病毒和病毒病重点实验室,北京102206 [2]北京化工大学生命科学与技术学院,北京100029

出　　处：《中华实验和临床病毒学杂志》2024年第4期402-408,共7页Chinese Journal of Experimental and Clinical Virology

摘　　要：目的研究基于乙型肝炎病毒核心蛋白的嵌合病毒蛋白纳米颗粒对肺腺癌动物模型的免疫治疗作用,为肺腺癌的纳米治疗技术提供依据。方法将人上皮细胞生长因子受体-2(human epidermal growth factor receptor-2,HER-2)B细胞抗原决定簇插入乙肝核心蛋白(hepatitis B core protein,HBc)的主要免疫显性区域(Major Immunodominant region,MIR),利用大肠杆菌进行表达纯化后,得到重组蛋白纳米颗粒HBc-HER2。将此重组蛋白纳米颗粒免疫小鼠肺腺癌皮下瘤模型,通过检测其血清中HER-2抗体水平及抗体型别,评价此纳米颗粒免疫原性。通过小鼠皮下瘤大小变化评价肿瘤治疗效果。结果得到了纯度较高的HBc-HER2重组蛋白,且电镜观察显示其形成了HBc-HER2纳米颗粒,动物实验表明免疫原性强,能够诱导机体产生高滴度的针对HER-2的抗体,并有良好的肿瘤治疗作用。结论基因重组的HBc-HER2在小鼠肺腺癌皮下瘤模型中有明显的抑制肿瘤作用,为肺腺癌的纳米治疗技术提供了依据。ObjectiveTo study the immunotherapeutic effect of chimeric hepatitis B core protein virus-like particles in subcutaneous lung adenocarcinoma mouse model,lays the foundation for the progression of tumor nano-therapeutic technology development.MethodsThe plasmid was constructed by inserting a B-cell epitope of the human epidermal growth factor receptor-2(HER-2)at hepatitis B core protein′s major immunodominant region(MIR).The recombinant virus nanoparticle,denoted as HBc-HER2,was obtained by E.coli expression system,followed by a series of purification steps.The immune response to this recombinant protein nanoparticle was assessed by measuring levels of anti-HER-2 antibody levels and characterizing antibody isotypes in a subcutaneous tumor mice model of lung adenocarcinoma.While tumor therapeutic efficacy was evaluated by measuring tumor size changes with an electronic caliper and MRI photography of subcutaneous tumor in mice.ResultsA high-purity HBc-HER2 recombinant protein was obtained and could assemble into nanoparticle.Animal studies had demonstrated the robust immunogenicity of this vaccine in inducing high levels of HER-2 specific antibodies,yielding positive therapeutic outcomes against tumors.ConclusionsThe engineered HBc-HER2 demonstrated notable tumor therapy efficacy in a subcutaneous lung adenocarcinoma mouse model,offering a foundation for tumor therapeutic nanotechnology vaccine research.

关 键 词：人类上皮细胞生长因子受体-2 乙肝核心蛋白病毒样颗粒 肿瘤免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]