IL-18基因修饰增强肿瘤细胞裂解物致敏的树突状细胞的抗肿瘤效应

目的:观察经肿瘤细胞裂解物致敏的白细胞介素18(IL-18)基因修饰的树突状细胞(DC)体内诱导的抗肿瘤免疫应答反应.方法:体外培养的小鼠骨髓树突状细胞经IL-18重组腺病毒感染后(IL18-DC),再经Hepal-6肝癌细胞裂解物冲击致敏后通过皮下注射用于荷瘤小鼠的治疗.用ELISA检测细胞因子,4 h51Cr释放法检测NK细胞活性及CTL杀伤活性.结果:致敏IL18-DC组体内诱导NK细胞活性与未致敏IL18-DC组无明显差别(P＞0.05),但明显高于致敏DC组和DC组(均P＜0.01);致敏IL18-DC组体内诱导特异性CTL杀伤活性明显高于IL18-DC组、致敏DC组和DC组(均P＜0.01);致敏IL18-DC组免疫治疗作用明显优于未致敏IL18-DC组、致敏DC组和DC组(均P＜0.01).结论:肿瘤细胞裂解物致敏的IL-18基因修饰的DC疫苗进行体内免疫治疗,能诱导出显著的抗肿瘤免疫反应,为DC介导的肿瘤基因治疗开辟了新的途径.

Antitumor Effects of Tumor Cell Lysate Sensitized Interleukin 18 Gene-modified Dendritic Cells

Objective: To investigate the induction of antitumor immune response of tumor cell lysate sensitized interleukin 18 gene-modified DC. Methods: The mice bone marrow-derived dendritic cells cultured in vitro were transfected by IL-18 recombinant adenovirus, and then were sensitized by hepatoma Hepal-6 cells lysate, and then were used to therapy of tumor-bearing mice in subcutaneous injection. Cytokines were assayed by ELISA, and NK cells and CTL activity were detected by 4h 51Cr releasing assay. Results: There was no difference between the sensitized group IL18-DC and the unsensitized group IL18-DC in the induction of NK cells activity(P>0.05), but NK cells activity of the sensitized group IL18-DC was significantly higher than the sensitized DC group and DC group(P<0.01). The immunotherapy effect of the sensitized group IL18-DC was significantly higher than the unsensitized IL18-DC group, the sensitized DC group and DC group, respectively(P<0.01). Conclusion: Tumor cell lysate sensitized interleukin 18 gene-modified DC could elicit potent antitumor responses in vivo,which will provide a new approach to the DC-mediated gene therapy for tumor.