硝基化通用T细胞表位疫苗CD47-NitraTh的设计与抑瘤活性  

Design and antitumor effect of nitrated T helper cell epitope vaccine CD47-NitraTh

作　　者：罗建华 夏雪霏 姚文兵 田浤 LUO Jianhua;XIA Xuefei;YAO Wenbing;TIAN Hong(Jiangsu Key Laboratory of Druggability of Biopharmaceuticals,School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学生命科学与技术学院江苏省生物药物成药性研究重点实验室

出　　处：《中国药科大学学报》2019年第5期614-621,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81573335,No.81673343,No.91753112)~~

摘　　要：利用遗传密码扩充技术,将免疫原性氨基酸对硝基苯丙氨酸定点引入到通用T细胞表位,并将其与免疫检查点分子CD47分子胞外区19-140片段融合表达,构建了靶向免疫检查点CD47的疫苗CD47-NitraTh。CD47-NitraTh能够在BALB/c小鼠体内诱导产生高滴度抗体,并可显著抑制CT26结肠癌肿瘤生长,提高脾脏CD4^+T细胞和CD8^+T细胞的比例,同时可促进naive T细胞向Th1细胞极化。值得关注的是,CD47-NitraTh不仅提高了肿瘤浸润淋巴细胞的比例,同时还降低了肿瘤组织中Treg细胞比例,意味着CD47-NitraTh疫苗能够重塑肿瘤免疫抑制性微环境。本研究结果提示,CD47-NitraTh可以作为有效的肿瘤疫苗候选分子。Using the genetic code extension technology,the immunogenic amino acid,p-nitrophenylalanine,was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140) to construct a vaccine targeting CD47.The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice,significantly inhibited CT26 colon cancer cells growth,and increased the ratio of spleen CD4^+ T cells and CD8^+ T cells.Meanwhile,it promoted the polarization of na?ve T cells to Th1 cells.Notably,CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues,which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment.The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.

关 键 词：免疫检查点 CD47 通用T细胞表位 肿瘤疫苗 

分 类 号：Q354[生物学—遗传学]