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目的 探讨白细胞介素 (IL) 2和B7 1双免疫基因转染肝癌细胞瘤苗免疫小鼠后获得的脾淋巴细胞经mIL 12基因修饰后治疗小鼠肝癌的可行性和疗效。方法 用 2 0 0PFU 细胞滴度的重组腺病毒载体 (Adv)将人IL 2和B7 1基因共同转染小鼠肝癌Hepal 6细胞株 ,经 80mg L丝裂霉素 (MMC)处理制备成肝癌细胞瘤苗 ,免疫同系小鼠后分离其脾淋巴细胞 (SLC) ,转染mIL 12基因 (Adv滴度 2 0 0PFU 细胞 )后注射入直径 1cm的小鼠皮下移植肝癌内 ,观察抗瘤效果。结果 转mIL 12基因SLC治疗组小鼠瘤体增加值最小 ( 0 .0 8± 0 .0 5 )cm3,与各对照组比差异有显著性 [(转染BGFP基因SLC、未转染SLC和生理盐水注射组分别为 ( 3 .46± 0 .15 ) ,( 3 .5 6± 0 .2 3)和( 8.12± 0 .5 4)cm3,P <0 .0 5 ]。结论 IL 2和B7 1双基因修饰肝癌瘤苗诱导小鼠产生的免疫脾淋巴细胞可能成为一种新的过继免疫治疗效应细胞及携带IL 12基因的载体细胞 ;基因治疗、特异性主动免疫和过继性细胞免疫治疗结合将有更优越的抗瘤效果。
Objective To investigate the feasibility and efficacy of splenic lymphocytes modified by mIL 12 gene in the treatment of mice with hepatocellular carcinoma after the transfection of hepatocellular carcinoma cell vaccine with interleukin (IL) 2 and B7 1 double immunization genes. METHODS: Human hepatoma cell line Hepal 6 was co-transfected with human IL 2 and B7 1 gene using a recombinant adenovirus vector (Adv) with a titer of 200 PFU. The hepatoma cells were treated with 80 mg L of mitomycin C (MMC) The tumor cells were isolated from the splenic lymphocytes (SLC) after immunization with the mice. The mIL 12 gene (Adv titer of 200 PFU cells) was transfected into mice with a diameter of 1 cm. The antitumor effect was observed. Results The added value of the tumor-bearing mice transfected with mIL 12 gene SLC was the smallest (0.08 ± 0.05) cm3, which was significantly different from that of the control group [(SLC transfected with BGFP gene and untransfected SLC (3.46 ± 0.15), (3.56 ± 0.23) and (8.12 ± 0.54) cm3 respectively, P <0.05) .Conclusion IL 2 and B7 1 double gene modified hepatocarcinoma vaccine induced immune-derived splenic lymphocytes in mice may become a new adoptive immunotherapy effector cells and carrier cells carrying IL 12 gene; gene therapy, specific active immunization and adoptive cellular immunotherapy Combination will have more superior antitumor effect.