不同途径免疫的AFP基因修饰DC瘤苗体内抗肿瘤效应的研究

The Therapeutic Effects of AFP Gene-Modified Dendritic Cell-Based Tumor Vaccine by Different Re-Infused Pathways

目的:探讨腺病毒介导AFP基因修饰的:DC(AFP—DC)瘤苗经不同途径免疫后机体抗肿瘤免疫应答反应。方法:采用皮下注射、静脉注射和瘤体注射三种途径回输AFP-DC瘤苗,比较观察AFP—DC瘤苗对荷瘤小鼠免疫治疗作用,应用4 h51Cr释放杀伤实验、T细胞与NK体内剔除实验等方法,观察AFP—DC瘤苗对荷瘤小鼠免疫治疗作用及保护性免疫反应。结果:皮下注射AFP-DC瘤苗治疗效果在抑制肿瘤生长、延长小鼠存活期方面都明显优于瘤体内注射或尾静脉注射(P<0.05),AFP-DC瘤苗体内能更有效地诱导特异CTL细胞毒活性,能使免疫动物产生一定的免疫保护作用,抵抗肿瘤细胞的再攻击。在AFP-DC瘤苗诱导抗肿瘤免疫排斥反应过程中,必需有CD4+T和CD8+T细胞的参与;而在其效应阶段,则依赖于CD8+T细胞的参与,CD4+T细胞为非必需;在免疫诱导及效应阶段剔除NK细胞对抗肿瘤免疫应答无明显影响。结论:皮下注射AFP-DC瘤苗能有效诱导机体产生抗肿瘤免疫反应,为DC介导的肝癌免疫治疗开辟了新的途径。

Objective: To observe the anti-tumor effects of adenovirus earring AFP gene transfected DC using different inculabe administrations. Methods: The immunotherapy effects of AFP-DC vaccine were compared among administration of intra-vein, hypo-dermal and intra-tumor. The protective and therapeutic effects of AFP-DC tumor vaccine were detected by 4 h 51Cr releasing assay and depleting T cells and NK cells. Results: The therapentic effect of Hypo-dermal was significantly better than assays of the other two ways in inhibiting tumor growth and prolonging the survival period of the mice(P <0. 05). AFP-DC tumor vaccine could more effectively induced specific CTL cytotoxicity, protective response, and resistance to the rechallenge of tumor cells. Both CD4 + and CD8 + T cells were required for AFP-DC tumor vaccine to induce antitumor immunological rejection. In the effective phase, antitumor immunological rejections were mainly depended on CD8+T cells, and CD4+ T cells were not necessary. Blocking NK cells in the induction and effect phase didn't have obvious influence on the antitumor immunity, suggesting that NK cells were not required for antitumor immunity induced by AFP-DC tumor vaccine. Conclusion: AFP-DC tumor vaccine by hypo-dermal administration could induce vaccine more efficient antitumor immune responses than intravein or intra-tumor ways in vivo, which provided new ways to the immunotherapy of tumor mediated by DC.