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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 tumor immunity indicate that effective antitumor immunity requires a synergistic effect of innate and acquired immunity. In our previous work, we successfully prepared leukemic vaccines modified by mouse β-defensin 2 (MBD2) and IL-18 genes and confirmed the anti-leukemic effects of both vaccines. In order to further enhance the anti-tumor effect, MBD2 and IL-18 were combined in mice to observe whether synergistic anti-leukemia and explore the mechanism. Tumorigenicity experiments confirmed that the combination of MBD2 and IL-18 combined tumor vaccine on tumorigenicity was significantly higher than that of MBD2 or IL-18 alone tumor vaccine (P <0.05); immune protection results showed that the combination of vaccination group 100 % Of the mice remained viable for long periods of time; treatment trials showed that the combination vaccine had a more significant therapeutic effect (P <0.05) than the MBD2 or IL-18 naïve tumor vaccine. The above results indicate that MBD2 and IL-18 combined vaccine can synergistically induce more effective anti-tumor immune response and immune protection. Mechanism of the study found that the combination of tumor vaccine can induce CTL cytotoxic activity of spleen lymphocytes and IFN-γ production was significantly enhanced. It is suggested that MBD2 and IL-18 may synergistically induce T cell proliferation and produce IFN-γ, so that the immune system can kill and clear leukemia cells more effectively.