双表达B7-1、B7-2基因肿瘤疫苗治疗小鼠肝癌优于单表达疫苗的研究

目的:研究B7-1、B7-2基因对肿瘤的免疫治疗作用。方法:应用转染有B7-1、B7-2基因的肝癌细胞株H22/B7-1、H22/B7-2,建立小鼠肝癌模型,观察小鼠成瘤期、荷瘤小鼠存活期及肿瘤结节大小。结果:各实验组动物都发生肿瘤,接种H22/B7-1 H22/B7-2组成瘤率低,对照组动物肿瘤呈进行性生长;组间成瘤潜伏期不同,与对照组相比,凡接种有H22/B7-2的小鼠肿瘤形成有迟发性;接种转B7基因细胞的小鼠肿瘤生长都较对照组慢;同时接种H22/B7-1和H22/B7-的小鼠能负载大于107的肿瘤细胞。转基因细胞在体外刺激淋巴细胞增殖和诱导CTLs的能力明显增强。结论:B7-1、B7-2都能增强肝癌细胞的免疫原性。B7-2在抗肿瘤早期发挥作用,B7-1随后起放大和调节作用。B7-1与B7-2联用效果优于单一应用。

Synergism of B7-1 and B7-2 transfectants enhance the antitumor immunity against mouse hepatocellular carcinoma

Objective: To study the combined effectiveness of B7-1 and B7-2-gene transfectants on the introduction of protectiveantitumor immunity against poorly immunogenic H22 mouse hepatocellular carcinoma (HCC)cells. Methods: A murine model forhepatocellular carcinoma, H22, was used to establish a model tumor vaccine. H22 cells were transfected with B7-1, B7-2, and stablelines were established. In vitro, H22 growth kinetics were measured. BALB/c mice were established by injected with exponentiallygrowing transfected cells variants for further research. The effect of gene transduction on anti-tumor immunity was studied.Lymphocytes proliferation was tested in vitro, and cytotoxic activity of CTL cells were evaluated by LDH assay; tumor size wasmeasured and survival time was recorded. Results: There was no difference in the growth rate of H22 and transfected cells variants invitro, and the growth of the respective tumor masses in vivo were similar. However, there was a difference in how soon afterinoculation in vivo that a mass could be detected. H22/B7-2 produced a measurable growing tumor cell mass later than others. And astronger and longer CTL activity and lymphocyte proliferation against H22/Wt cells were obtained after combination use of B7-1 andB7-2 than using each single transfectant. Conclusion: The combination of immunization of B7-1 and B7-2-transfected HCC cellscould induce full, long-lasting tumor immunogenicity preventing tumor development. The cells transfected with B7-1 in combinationwith B7-2 is more effective than those transfected with either B7-1 or B7-2 molecules alone in conferring antitumor immunogeniicity.