基于M2与OK-432的肿瘤细胞裂解物致敏的树突状细胞疫苗抗小鼠Lewis肺癌作用研究  

Anti-Lewis Lung Cancer Immunity by Tumor Cell Lysate-sensitized Dendritic Cell Vaccines with M2 and OK-432 in Mice

作　　者：葛驰宇[1,2] 周舟[3] 张君丽[1] 

机构地区：[1]江苏食品药品职业技术学院医药与健康管理学院江苏省蛋白质类药物工程实验室,淮安223003 [2]中国药科大学微基因药学实验室,南京210009 [3]扬州大学医学院药学系,扬州225001

出　　处：《药学与临床研究》2016年第2期97-102,共6页Pharmaceutical and Clinical Research

基　　金：先声药业研究生创新基金(CX10B-004XS)

摘　　要：目的建立增强肺癌细胞裂解物（L）致敏的树突状细胞（D）疫苗（L-D）免疫临床治疗肺癌效果的方法.方法：以来源于热休克蛋白70第407-426的两段重复序列（M）和OK-432（O）为佐剂刺激Lewis肺癌细胞裂解物,制备了树突状细胞疫苗LMO-D.结果：与L-D相比,LMO-D显著增加CD11c、CD40、CD80、CD86、MHC-Ⅰ和Ⅱ等细胞表面抗原的表达;LMO-D免疫荷瘤小鼠后,显著增强Th1类细胞因子肿瘤坏死因子α和干扰素γ,而不增强Th2类细胞因子白介素-5的表达;T淋巴细胞增殖诱导显著和淋巴细胞毒反应; 此外LMO-D显著降低荷瘤小鼠瘤重与体积,延长了荷瘤小鼠的生存期.结论：LMO-D可通过诱导显著的T细胞免疫反应有效抑制肿瘤生长.Objective: To establish a new method for improving the anti-lung cancer clinical efficacy of dendritic cell vaccines sensitized by lung cancer tumor cell lysate(L-D). Methods: Two tandem repeats of hot shock protein 70 peptide epitope 407-426(M) and OK-432(O) was introduced to Lewis tumor cell lysate to produce LMO-D. Results: Compared with L-D, LMO-D remarkably increased the expression of cell surface markers CD11 c, CD40, CD80, CD86, MHC- Ⅰ and Ⅱ, enhanced the excretion of Th1-type cytokines TNF-α and IFN-γ but not Th2-type cytokines IL-5, and significantly induced the proliferation and cytotoxicity of T lymphocytes. Besides, tumor-bearing mice immunized with LMO-D resulted with decreased tumor weight, reduced tumor volume and prolonged survival. Conclusion: LMO-D can effectively inhibit the growth of Lewis lung cancer in mice by inducing T cell responses.

关 键 词：LEWIS肺癌 树突状细胞疫苗 M2 OK-432 

分 类 号：R967[医药卫生—药理学]