小鼠β-防御素2与白介素18肿瘤疫苗的协同抗白血病作用研究

Synergistic antitumor effect in a murine leukemia model by combinational gene therapy using murine beta defensin 2 and IL-18

肿瘤免疫方面的最新进展表明,有效的抗肿瘤免疫需要天然免疫和获得性免疫的协同作用。我们在前期工作中成功制备了小鼠β-防御素2(MBD2)和IL-18基因修饰的白血病疫苗,并证实了两种瘤苗的抗白血病作用。为了进一步增强抗肿瘤效果,本实验将MBD2和IL-18瘤苗联合应用于小鼠体内,观察是否具有协同抗白血病作用并探索机制。致瘤性实验证实,MBD2与IL-18联合瘤苗对致瘤性的抑制作用明显高于MBD2或IL-18单独瘤苗(P<0.05);免疫保护作用结果显示,联合瘤苗接种组100%小鼠仍可长期存活;治疗实验显示,与MBD2或IL-18单独瘤苗相比,联合瘤苗具有更显著的治疗效果(P<0.05)。上述结果表明,MBD2和IL-18联合瘤苗可协同诱导更有效的抗肿瘤免疫反应和免疫保护作用。机制探讨发现,联合瘤苗能诱导脾脏淋巴细胞的CTL杀伤活性以及IFN-γ产生明显增强。提示,MBD2和IL-18可能协同诱导T细胞增殖,产生IFN-γ,使免疫系统能更有效地杀伤清除白血病细胞。

Recent advances in our standing on tumor immunology suggest that the most effective immune response to cancers requires the coordinated action of both the innate and the acquired arms of the immune system.We have previously demonstrated that vaccine with murine β-defensin 2(MBD2) and interleukin-18(IL-18) elicited potent antileukemia responses in the L1210 murine model.As MBD2 and IL-18 appear to function on different components required by an effective antitumor immune response including both innate and ad...