HCA587/MAGE-C2蛋白疫苗免疫记忆效应及应答持久性的研究  

Immunological memory effect and immune response persistence of HCA587/MAGE-C2 protein vaccine

作　　者：陈惠媛 焦薇 张丽洁[3] 杨伟明[1] 陈娟娟[1] 尹艳慧 CHEN Huiyuan;JIAO Wei;ZHANG Lijie;YANG Weiming;CHEN Juanjuan;YIN Yanhui(Department of Clinical Laboratory,Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Key Laboratory of Medical Immunology of Ministry of Health,Department of Immunology,Peking University Health Science Center,Beijing 100191,China;Institute of Hematology,Shaanxi Provincial People’s Hospital,Xi'an 710068,China)

机构地区：[1]南昌大学第二附属医院检验科,330006 [2]北京大学医学部免疫系,100191 [3]陕西省人民医院血液研究所,西安710068

出　　处：《免疫学杂志》2022年第9期818-824,共7页Immunological Journal

基　　金：国家自然科学基金(81960497);江西省青年科学基金(20181BAB215026;20192BAB215016);江西省教育厅青年基金(GJJ170154);江西省卫生健康委员会(20201061)。

摘　　要：目的探究HCA587/MAGE-C2蛋白疫苗的免疫记忆效应,并监测其应答的持久性。方法在C57BL/6小鼠右侧胁腹部皮下接种B16-HCA587肿瘤细胞建立荷瘤小鼠模型。采用酶联免疫斑点试验(ELISpot)法检测脾细胞产生IFN-γ的频率;采用酶联免疫吸附实验(ELISA)法检测抗HCA587特异性抗体;采用游标卡尺测量肿瘤大小。结果接种B16-HCA587肿瘤细胞后,第7天给予HCA587蛋白疫苗治疗效果优于第12天,表现为荷瘤小鼠肿瘤生长缓慢,生存期显著延长。该疫苗二次免疫后第14天接种B16-HCA587肿瘤细胞预防效果优于第7天,表现为疫苗预防组小鼠第60天未成瘤率100%,到120天未成瘤率仍有83%(P<0.0001)。该疫苗诱导的细胞免疫应答可在小鼠体内持续至少24周,抗HCA587抗体滴度在24周仍保持较高水平。在首次治疗模型中疫苗治疗后40 d仍未成瘤的小鼠,再次接受3倍于首剂量的肿瘤细胞时,仍可表现出显著的肿瘤生长缓慢和生存期延长。结论HCA587蛋白疫苗于二次免疫后14天对HCA587阳性的荷瘤小鼠的肿瘤治疗与预防效果强大而特异,而且其持久且高强度的免疫记忆可保护小鼠免受肿瘤的二次攻击。Immunological memory is a crucial component of vaccine-induced anti-tumor immunotherapy.Therefore,this study was designed to investigate the immunological memory effect and immune response persistence of the HCA587/MAGE-C2 protein vaccine.In this study,a tumor model was established by subcutaneous inoculation of B16-HCA587 tumor cells into the right flank of C57BL/6 mice.The frequency of IFN-γ-producing splenocytes was measured by ELISpot;the HCA587-specific antibody was measured by ELISA;the size of tumor was measured with vernier caliper.Data showed that after vaccination with B16-HCA587 tumor cells,treatment with HCA587 protein vaccine on day 7 was superior to that on day 12,as indicated by slower tumor growth and significantly longer survival of tumor bearing mice.Vaccination with B16-HCA587 tumor cells on day 14 after the secondary immunization of this vaccine had a better preventive effect than that on day 7,as indicated by the 100%non-tumorigenic rate on day 60 and the 83%non-tumorigenic rate on day 120 in mice of the vaccine prophylactic group(P<0.0001).The cellular immune response induced by this vaccine could last for at least 24 weeks in mice,and the anti-HCA587 antibody titers remained high at week 24.After rechallenged by 3 times the first dose of tumor cells,the mice remained non-tumorigenic for 40 days after vaccine treatment in the first treatment model still exhibited significantly slower tumor growth and prolonged survival.Collectively,the tumor treatment and prophylactic effect of HCA587 protein vaccine on HCA positive tumor bearing mice at 14 days after secondary immunization was robust and specific,and its long-lasting and high-intensity immunological memory protect mice from the rechallenge of tumors.

关 键 词：肿瘤免疫治疗 癌症睾丸抗原 HCA587蛋白疫苗 免疫记忆 二次攻击 

分 类 号：R392.12[医药卫生—免疫学]