CTP介导的EGFRvⅢ肽疫苗诱导特异性免疫应答抑制脑胶质瘤的研究  

Specific immune response induced by CTP mediated EGFRvⅢ peptide vaccine inhibits glioma

作　　者：许琼冠[1] 欧阳一彬 谢镇明 XU Qiongguan;OUYANG Yibin;XIE Zhenming(Department of NeurosurgeryⅡ,Second Affiliated Hospital of Hainan Medical College,Haikou 571103,China)

机构地区：[1]海南医学院第二附属医院神经外科二区,海口571103

出　　处：《中国免疫学杂志》2022年第18期2231-2235,共5页Chinese Journal of Immunology

基　　金：海南省卫生健康行业科研项目(19A200024)。

摘　　要：目的:探索CTP修饰的EGFRvⅢ多肽疫苗是否可激活体内抗肿瘤免疫应答并抑制胶质瘤生长。方法:qPCR检测胶质瘤患者肿瘤和癌旁组织EGFR和EGFRvⅢ表达;荧光显微镜观察多肽疫苗CTP-V2在树突状细胞(DCs)中的定位情况;流式细胞术检测负载多肽疫苗DCs与CD8^(+)T细胞共孵育后T细胞增殖及CD69表达;体内抑瘤实验检测CTP-V2的体内抗肿瘤活性;免疫组织化学检测T细胞肿瘤浸润及肿瘤细胞凋亡情况。结果:qPCR结果显示,胶质瘤患者肿瘤组织中EGFR表达较癌旁组织显著升高(P<0.001),肿瘤组织EGFR和EGFRvⅢ表达呈正相关(R=0.58),且EGFR和EGFRvⅢ表达与胶质瘤患者不良预后相关;显微镜观察显示,CTP-V2可有效定位于DCs胞质区域;流式检测结果表明负载CTP-V2的DCs较负载V2的DCs可更显著地刺激CD8^(+)T细胞增殖(P<0.000 1)和CD69表达(P<0.000 1);小鼠移植瘤模型显示,CTP-V2可显著抑制胶质瘤生长(P<0.01),同时可明显增加T细胞肿瘤浸润(P<0.001),促进肿瘤细胞凋亡(P<0.001)。结论:CTP-V2可有效激活机体抗肿瘤免疫应答,抑制胶质瘤生长,可能是治疗胶质瘤的新策略。Objective:To explore whether CTP modified EGFRvⅢpolypeptide vaccine can activate anti-tumor immune response and inhibit growth of glioma.Methods:Expressions of EGFR and EGFRvⅢin cancer tissues and paracancerous tissues of glioma patients were detected by qPCR.Localization of polypeptide vaccine CTP-V2 in dendritic cells(DCs)was observed by fluores⁃cence microscope.Flow cytometry was used to detect proliferation and CD69 expression of T cells after DCs loaded with polypeptide vaccine were incubated with CD8^(+)T cells.Anti-tumor activity of CTP-V2 in vivo was detected by tumor inhibition in vivo.T cell tumor infiltration and tumor cell apoptosis were detected by immunohistochemistry.Results:qPCR results showed that expression of EGFR in tumor tissue of glioma patients was significantly higher than that in paracancerous tissues(P<0.001).Expressions of EGFR with EGFRvⅢin tumor tissue was positively correlated(R=0.58),and expressions of EGFR and EGFRv Ⅲ were related to poor prognosis of gliomapatients.Microscopic observation showed that CTP-V2 could be effectively localized in cytoplasmic region of DCs.Flow cytometry results showed that DCs loaded with CTP-V2 could stimulate proliferation of CD8^(+)T cells(P<0.0001)and expression of CD69(P<0.0001)than DCs loaded with V2.Mouse transplanted tumor model showed that CTP-V2 could significantly inhibit growth of glioma(P<0.01),significantly increase tumor infiltration of T cells(P<0.001)and promote apoptosis of tumor cells(P<0.001).Conclusion:CTP-V2 can effectively activate anti-tumor immune response and inhibit growth of glioma,which may be a new strategy for treatment of glioma.

关 键 词：胶质瘤 CTP 多肽疫苗 免疫治疗 

分 类 号：R739.41[医药卫生—肿瘤]