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骨髓来源的抑制性细胞(myeloid derived suppressor cell,MDSC)在肿瘤免疫逃逸中扮演着重要的角色,普遍认为清除MDSC将有助于阻止肿瘤的生长。因此,本研究以霍乱毒素B亚基(CTB)五聚体为载体构建了一种靶向小鼠MDSC表面标识蛋白S100A8的重组多肽疫苗CTB-S100A8,并在大肠杆菌分泌表达系统中获得表达。经纯化后的重组CTB-S100A8五聚体蛋白辅以氢氧化铝佐剂免疫小鼠后能打破自身免疫耐受产生高滴度的S100A8抗体。在4T1小鼠乳腺癌肿瘤模型中,CTB-S100A8疫苗能够有效阻止肿瘤生长,并减少外周血中肿瘤诱导的单核细胞来源的MDSC。而正常的髓系来源MDSC、树突状细胞和巨噬细胞不受其影响。研究表明,CTB-S100A8是一种良好的靶向肿瘤诱导的MDSC的重组疫苗,具有较大的临床应用潜力。
Bone marrow-derived myeloid derived suppressor cells (MDSCs) play an important role in tumor immune escape. It is generally accepted that the removal of MDSCs will help prevent tumor growth. Therefore, in this study, CTB-S100A8, a recombinant polypeptide vaccine targeting mouse MDSC surface marker protein S100A8, was constructed using cholera toxin B subunit (CTB) pentamer as a vector and expressed in E. coli secretion expression system. The purified recombinant CTB-S100A8 pentameric protein supplemented with aluminum hydroxide adjuvant to immunize mice can break down autoimmune tolerance to produce high titer S100A8 antibody. In the 4T1 mouse breast tumor model, the CTB-S100A8 vaccine effectively prevented tumor growth and reduced tumor-induced monocyte-derived MDSCs in peripheral blood. While normal myeloid derived MDSCs, dendritic cells and macrophages are unaffected by them. Studies have shown that CTB-S100A8 is a good recombinant vaccine that targets tumor-induced MDSCs and has great potential for clinical application.