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

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。

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

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 CD11c, 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.