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目的研究基于恒定链的丙型肝炎病毒(HCV)NS3内源性靶向巨噬细胞表面分子Ia的分子基因疫苗对HCV NS3荷瘤小鼠的抑瘤效果,探索HCV感染基因治疗的可行途径。方法BALB/c小鼠皮下接种稳定表达HCV NS3的小鼠骨髓瘤SP2/0-NS3细胞,3 d后于股四头肌注射疫苗进行免疫治疗,2周后进行一次加强免疫。BALB/c小鼠共64只,随机分为等渗盐水对照组、空质粒pCI-neo对照组、pHCV- NS3非靶向治疗组和pHCV-NS3-Thl靶向治疗组,观察成瘤时间、肿瘤大小和小鼠的60 d存活率。结果等渗盐水、pCI-neo、pHCV-NS3、pHCV-NS3-Th1组小鼠平均成瘤时间分别为(16.17±2.55)d、(14.40 ±1.82)d、(16.75±2.36)d、(24.00±5.57)d;成瘤率分别为100.0%(13/13)、100.0%(14/14)、57.1%(8/14)和46.7%(7/15);60 d存活率分别为0、0、50.0%(7/14)和53.3%(8/15)。对四个时间点成瘤小鼠肿瘤大小比较的结果显示,pHCV-NS3-Th1组成瘤小鼠的肿瘤直径最小,与其他组相比,差异均有统计学意义(P<0.01)。结果显示,成瘤小鼠的平均存活时间比等渗盐水组延长6 d,比pCI-neo组延长12 d(P<0.05),比pHCV-NS3组延长6 d。结论pHCV-NS3-Th1具有延迟HCV-NS3荷瘤小鼠肿瘤形成、限制肿瘤生长、降低成瘤率、病死率以及提高存活率的作用。基于恒定链的内源性靶向性基因疫苗有望作为HCV感染防治的候选治疗性疫苗。
Objective To study the antitumor effect of molecular gene vaccine based on constant chain-linked hepatitis C virus NS3 endogenous macrophage-derived macrophage surface molecule Ia on HCV NS3 tumor-bearing mice and to explore possible ways of gene therapy for HCV infection. Methods BALB / c mice were subcutaneously inoculated with mouse myeloma SP2 / 0-NS3 cells stably expressing HCV NS3. After 3 days, immunized mice were vaccinated with quadriceps femoris and boosted two weeks later. A total of 64 BALB / c mice were randomly divided into saline control group, empty plasmid pCI-neo control group, pHCV-NS3 non-target therapy group and pHCV-NS3-Thl target therapy group. Tumor size and 60-day survival in mice. Results The average tumorigenic time of mice in isotonic saline, pCI-neo, pHCV-NS3 and pHCV-NS3-Th1 groups was (16.17 ± 2.55) days and (14.40 ± 1.82 days) ± 5.57) d. The tumorigenic rates were 100.0% (13/13), 100.0% (14/14), 57.1% (8/14) and 46.7% (7/15) 0, 50.0% (7/14) and 53.3% (8/15). The tumor size of tumor-bearing mice at four time points showed that the tumor diameter of pHCV-NS3-Th1 mice was the smallest, which was significantly different from other groups (P <0.01). The results showed that the mean survival time of tumor-bearing mice was prolonged by 6 d compared with that of saline-naive group, which was 12 d longer than that of pCI-neo group (P <0.05) and 6 d longer than that of pHCV-NS3 group. Conclusion pHCV-NS3-Th1 can delay the tumor formation, limit the tumor growth, reduce the tumorigenicity, mortality and improve the survival rate of HCV-NS3 tumor-bearing mice. Endogenous targeted gene vaccines based on a constant strand are expected to be candidate therapeutic vaccines for the prevention and treatment of HCV infection.