HCA587/MAGE-C2蛋白联合CFA和CpG佐剂的免疫应答及抗肿瘤效应  

Immune response and antitumor effects of HCA587/MAGE-C2 protein formulated with CFA and CpG

作　　者：焦薇 谭媛芳 陈惠媛 范秋颖 尹艳慧 陈娟娟[1] JIAO Wei;TAN Yuanfang;CHEN Huiyuan;FAN Qiuying;YIN Yanhui;CHEN Juanjuan(Jiangxi Province Key Laboratory of Laboratory Medicine,Department of Clinical Laboratory,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Immunology,Peking University Health Science Center,Beijing 100191,China)

机构地区：[1]南昌大学第二附属医院检验科,江西省检验医学重点实验室,南昌330006 [2]北京大学医学部免疫系,北京100191

出　　处：《中国免疫学杂志》2024年第3期572-576,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金(82160314,81960497)。

摘　　要：目的:探究HCA587/MAGE-C2蛋白在不同免疫策略下诱导抗原特异性免疫应答的能力及在小鼠模型中的抗肿瘤作用。方法:HCA587蛋白与弗氏完全佐剂(CFA)/弗氏不完全佐剂(IFA)、不同剂量CpG ODN 1826(CpG)联合免疫C57BL/6J小鼠,比较不同方案诱导的细胞免疫和体液免疫水平。酶联免疫斑点试验(ELISpot)检测脾细胞产生IFN-γ的频率;ELISA检测抗HCA587特异性抗体;流式细胞术分析胞内细胞因子染色(ICCS)。将B16-HCA587肿瘤细胞皮下接种于C57BL/6J小鼠右侧胁腹部建立荷瘤小鼠模型,采用免疫比较方案中细胞和体液免疫应答最强的策略进行治疗;游标卡尺测量肿瘤体积;Log-rank检验评估生存曲线。结果:HCA587蛋白联合CFA和50μg CpG免疫方案诱导出能分泌抗原特异性IFN-γ的脾细胞频数最多,诱导抗HCA587的IgG抗体滴度最高,诱导出的IFN-γ^(+)CD4^(+)T细胞比例最高(P<0.05)。肿瘤治疗模型中,HCA587蛋白联合CFA和50μg CpG可显著抑制肿瘤生长(P=0.026),但Log-rank检验显示其对生存期无明显影响(P>0.05)。结论:佐剂CFA和50μg CpG联合组成的HCA587蛋白疫苗在小鼠模型中能诱导强大的细胞免疫应答和体液免疫应答,并具有一定抗肿瘤作用,为肿瘤抗原蛋白疫苗临床前研究提供了新的实验数据。Objective:To investigate ability of HCA587/MAGE-C2 protein combined with different adjuvants inducing antigen-specific immune response and antitumor effects in mice model.Methods:C57BL/6J mice were immunized with HCA587 protein com-bined with Freund's complete adjuvant(CFA)/Freund's incomplete adjuvant(IFA)and different doses of CpG ODN 1826(CpG),cellular and humoral immunity levels induced by different schemes were compared.ELISpot was used to evaluate frequency of IFN-γ-producing splenocytes.HCA587-specific antibodies were detected by ELISA.Intracellular cytokine staining(ICCS)analysis was mea-sured by flow cytometry.A tumor-bearing animal model was created by subcutaneously injection of B16-HCA587 tumor cells into right flank of C57BL/6J mice,which was treated with strategy with the strongest cellular and humoral immune response in immune compari-son protocol.Vernier calipers were used to measure tumor volume,and Log-rank test was used to analyze survival curve.Results:HCA587 protein combined with CFA and 50μg CpG elicited strongest specific IFN-γ-secreting splenocytes and anti-HCA587 anti-bodies,which induced highest IFN-γ^(+)CD4^(+)T cells(P<0.05).In tumor treatment model,HCA587 protein combined with CFA and 50μg CpG significantly inhibited tumor growth(P=0.026),while Log-rank test showed no significant effect on survival(P>0.05).Conclusion:HCA587 protein vaccine formulated with CFA and 50μg CpG causes a significant cellular and humoral immune response and partial antitumor effect in mice model,providing new experimental data for preclinical research of tumor antigen protein vaccine.

关 键 词：HCA587蛋白 佐剂 IFN-Γ CD4^(+)T细胞 抗肿瘤作用 

分 类 号：R392.9[医药卫生—免疫学]