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免疫检查点B7-H3表位疫苗的设计及其抗肿瘤活性
引用本文:夏雪霏,张莉,罗建华,姚文兵,高向东,田浤. 免疫检查点B7-H3表位疫苗的设计及其抗肿瘤活性[J]. 中国药科大学学报, 2021, 52(4): 472-479
作者姓名:夏雪霏  张莉  罗建华  姚文兵  高向东  田浤
作者单位: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,新疆医科大学第一附属医院,乌鲁木齐 830054,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,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,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,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
基金项目:国家自然科学基金资助项目(No.81973222,No.82073754);新疆自治区重点研发计划项目(No.2020B03003-2)
摘    要:B7-H3是在多种肿瘤表面过表达的免疫检查点分子,是肿瘤免疫治疗的理想靶点。利用本实验室前期设计的硝基化T细胞表位为基础,构建了可靶向免疫检查点B7-H3的表位疫苗。该疫苗能在CT26结肠癌模型中显著抑制肿瘤生长,且与PD-L1蛋白疫苗有明显的协同作用。B7-H3疫苗可以增加脾脏T淋巴细胞中CD4+ T细胞的比例和肿瘤浸润T淋巴细胞中CD8+ T细胞的比例,同时减少肿瘤浸润CD4+ T淋巴细胞中抑制性Treg细胞的比例,有效改善肿瘤免疫抑制微环境。研究结果提示,B7-H3表位疫苗可以作为有效的肿瘤疫苗候选分子。

关 键 词:免疫检查点  B7-H3  表位疫苗  肿瘤免疫
收稿时间:2021-03-19
修稿时间:2021-06-28

Design and antitumor activity of immune checkpoint B7-H3 epitope vaccine
XIA Xuefei,ZHANG Li,LUO Jianhu,YAO Wenbing,GAO Xiangdong and TIAN Hong. Design and antitumor activity of immune checkpoint B7-H3 epitope vaccine[J]. Journal of China Pharmaceutical University, 2021, 52(4): 472-479
Authors:XIA Xuefei  ZHANG Li  LUO Jianhu  YAO Wenbing  GAO Xiangdong  TIAN Hong
Affiliation:Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009,The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China,Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009,Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009,Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009,Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009
Abstract:B7-H3 is an immune checkpoint molecule overexpressed on the surface of a variety of tumors, and is is an ideal target for tumor immunotherapy. In this study, nitrolated T cell epitope designed in the early stage of the laboratory was used to construct an epitope vaccine that can target immune checkpoint B7-H3. The vaccine can significantly inhibit tumor growth in the CT26 colon cancer model, and has a significant synergistic effect with the PD-L1 protein vaccine. B7-H3 vaccine can increase the proportion of CD4+ T cells in splenic T lymphocytes and the proportion of CD8+ T cells in tumor-infiltrating T lymphocytes, while reducing the proportion of suppressor Treg cells in tumor-infiltrating CD4+ T lymphocytes, which effectively improves tumor immunosuppressive microenvironment. Research results suggest that the B7-H3 epitope vaccine can be used as an effective tumor vaccine candidate molecule.
Keywords:immune checkpoint  B7-H3  epitope vaccine  tumor immunity
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