IL-15联合肿瘤全细胞疫苗抗小鼠结肠癌的实验研究  

IL-15 Enhance the Therapeutic Effects of Whole Cell Vaccine in Mouse CT26 Colon Carcinoma Model

作　　者：赵玉伟[1] 李知勉[1] 赵成建[1] 张凌[1] 金璐[1] 王晓飞[1] 杨寒朔[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室,成都610041

出　　处：《四川大学学报（医学版）》2010年第4期567-570,594,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家973计划(项目编号2004CB518800)资助

摘　　要：目的研究IL-15能否协助肿瘤全细胞疫苗诱发有效的抗肿瘤免疫反应。方法建立小鼠皮下CT26结肠癌模型,将32只荷瘤小鼠随机分为4组:对照组(200μL PBS)、CT26疫苗组(200μL细胞疫苗,含2×106细胞)、mIL-15组(200μL脂质体-质粒DNA复合物,含20μg pORF9-mIL-15质粒)和CT26+mIL-15联合治疗组〔100μL脂质体-质粒DNA复合物(20μg pORF9-mIL-15质粒)和100μL细胞疫苗(2×106细胞)〕。阳离子脂质体按3∶1的比例包裹真核表达质粒pORF9-mIL-15制成纳米复合物。各组小鼠采用皮下多点注射的方式进行治疗,定时观察各组小鼠肿瘤生长情况并测量肿瘤体积。实验结束时取肿瘤进行组织病理学观察及肿瘤组织原位凋亡检测。结果 CT26+mIL-15组小鼠肿瘤的生长受到抑制,抑瘤率为45%,与其他3组比较差异有统计学意义(P<0.05);肿瘤组织病理学分析显示CT26+mIL-15组小鼠肿瘤内部坏死区域较其他3组明显增多;肿瘤组织原位凋亡检测显示CT26+mIL-15组小鼠肿瘤内部细胞凋亡增多,凋亡指数为(46.7±7.2)%,与对照组(4.9±1.4)%、CT26疫苗组(5.4±1.4)%和mIL-15组(15.6±4.2)%比较,差异有统计学意义(P<0.05)。结论 IL-15能够增强全细胞疫苗的免疫治疗效果。Objective To determine the enhancement effects of IL-15 to the tumor whole cell vaccine in tumor immunotherapy.Methods CT26 colon carcinoma model was established with BALB/c mice.Thirty two mice with CT26 colon carcinoma were divided randomly into four groups,which were subcutaneouly injected at several spots with PBS(200 μL),CT26 whole cell vaccine(2×106cells in 200 μL PBS),mIL-15(20 μg,encapsulated with liposome in 200 μL 5% glucose solution) and CT26 whole cell vaccine(2×106cells in 100 μL PBS) plus mIL-15(20 μg,encapsulated with liposome in 100 μL 5% glucose solution) respectively every three days for six doses,the plasmid was injected beside the vaccine injecting spots.The size of tumors was measured every four days.All mice were sacrificed 30 days after tumor implantation.The pathologic observation and apoptotic analysis of tumors were preceded.Results CT26 whole cell vaccine combined with mIL-15 inhibited tumor growth by 45% compared with that of control group,the differences between CT26+mIL-15 group and the other three groups were significant(P<0.05).The HE staining showed that the necrosis areas in tumors of the CT26+mIL-15 group were larger than those of other three groups.The apoptotic index of tumors from the CT26+mIL-15 group was(46.7±7.2)%,higher than that of the other three groups obviously(P<0.05).Conclusion IL-15 could enhance the therapeutic effects of CT26 whole cell vaccine in tumor immunotherapy.

关 键 词：全细胞疫苗 IL-15 结肠癌 免疫治疗 

分 类 号：R735.3[医药卫生—肿瘤]