基于硝基化T细胞表位的PD-L1疫苗佐剂的筛选  

Screening of adjuvant for PD-L1 vaccine based on nitrated T cell epitope

作　　者：周虹佑 高向东 姚文兵 田浤 ZHOU Hongyou;GAO Xiangdong;YAO Wenbing;TIAN Hong(Jiangsu Key Laboratory of Druggability of Biopharmaceuticals,School of Life Science and Technology,China Pharmaceutical University,Nanjing 211198,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,南京211198

出　　处：《中国药科大学学报》2024年第3期397-403,共7页Journal of China Pharmaceutical University

基　　金：国家自然科学基金项目(No.81973222,No.82073754);新疆维吾尔自治区重点研发计划项目(No.2020B03003)。

摘　　要：为了充分发挥本课题组前期设计的基于硝基化T表位的靶向PD-L1的肿瘤疫苗(PD-L1-NitraTh)的抑瘤活性,选择了作用机制不同的几种佐剂进行比较,以期筛选出最适用于此类疫苗的佐剂。研究结果显示,Poly(I:C)、CPG1018、肿节风多糖SGP2及GM-CSF等佐剂均可以提高PD-L1-NitraTh疫苗的免疫原性,其中,Poly(I:C)组诱导产生的抗体滴度最高。对T细胞分化相关转录因子的qPCR检测结果显示,Poly(I:C)减少了GATA3和FoxP3的表达,提示对CD4^(+)T细胞分化有较强的影响。同时,相比其他佐剂,Poly(I:C)可以辅助PD-L1-NitraTh增加肿瘤内T淋巴细胞以及CD11b^(+)细胞浸润,提示Poly(I:C)佐剂可能适用于以硝基化T表位为基础的肿瘤疫苗。To enhance the anti-tumor activity of tumor vaccine targeting PD-L1 based on the nitrated T-epitope(PD-L1-NitraTh),this research compared several adjuvants with different mechanisms to screen out the adjuvant most suitable for PD-L1-NitraTh.The results showed that Poly(I:C),CPG1018,swollen knotted polysaccharide SGP2 and GM-CSF could enhance the immunogenicity of PD-L1-NitraTh when used as adjuvants,with the Poly(I:C)group inducing the highest antibody titer.The results of qPCR for T cell differentiation-related cytokines showed that Poly(I:C)reduced the expression of GATA3 and FoxP3,indicating a strong effect on CD4^(+)T cell differentiation.Besides,compared with other adjuvants,Poly(I:C)could assist PD-L1-NitraTh to increase the infiltration of T cells as well as CD11b^(+)cells within tumor,suggesting that Poly(I:C)may be the suitable adjuvant for tumor vaccines based on the nitrated T epitopes.

关 键 词：肿瘤疫苗 佐剂 TOLL样受体 Poly(I:C) 

分 类 号：R186[医药卫生—流行病学] R967[医药卫生—公共卫生与预防医学]