EGFRvⅢ与HBcAg重组疫苗抗肿瘤作用的实验研究

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目的:观察PEP-3/HBcAg融合蛋白疫苗的体内抗肿瘤作用。方法:BALB/c小鼠30只随机分成3组,分别接种PEP-3/HBcAg融合蛋白、HBcAg和生理盐水,待融合蛋白组小鼠体内抗体效价达到1:20000时终止免疫,于每只小鼠背部皮下种植阳性Renca细胞,2×105个/只。观察融合蛋白疫苗的抗肿瘤效应。采用HE染色和免疫组织化学图像分析法检测各组肿瘤组织的坏死情况和EGFRvIII表达水平。结果:融合蛋白组、HBcAg组和生理盐水组的成瘤率分别为50%、100%和100%。生理盐水组肿瘤生长速度最快,HBcAg组次之,融合蛋白组肿瘤出现最晚,生长速度最慢。融合蛋白组成瘤小鼠肿瘤平均质量显著小于生理盐水组和HBcAg组(t=4·731,P=0·044;t=6·890,P=0·040);后两组肿瘤质量无统计学意义(t=0·024,P=0·382)。HBcAg组和生理盐水组移植瘤呈不完全小片状坏死,融合蛋白组移植瘤呈大片状坏死,伴炎细胞浸润。融合蛋白组EGFRvⅢ表达水平明显低于生理盐水组和HBcAg组(t=3·157,P=0·006;t=2·539,P=0·021),后两者EGFRvIII表达水平无统计学差异(t=0·460,P=0·651)。结论:PEP-3/HBcAg融合蛋白疫苗能诱导机体产生保护性免疫反应,并具有抗肿瘤作用。 Objective: To observe the anti-tumor effect of PEP-3/HBcAg fusion protein vaccine in vivo. METHODS: Thirty BALB/c mice were randomly divided into 3 groups and inoculated with PEP-3/HBcAg fusion protein, HBcAg, and saline. When the antibody titer in the fusion protein group reached 1:20000, the immunization was terminated. Positive Renca cells were implanted subcutaneously on the back of the mice, 2 x 105 cells/body. Observe the anti-tumor effect of the fusion protein vaccine. HE staining and immunohistochemical image analysis were used to detect the necrosis and EGFRvIII expression levels of tumor tissues in each group. Results: The tumor formation rates of the fusion protein group, the HBcAg group, and the saline group were 50%, 100%, and 100%, respectively. The tumors in the saline group had the fastest growth rate, followed by the HBcAg group. The tumors in the fusion protein group were the latest, and the growth rate was the slowest. The average tumor mass of tumor mice composed of fusion protein was significantly smaller than that of saline group and HBcAg group (t=4.731, P=0.044; t=6.890, P=0.040); the tumor quality was not statistically significant in the latter two groups. Significance (t=0.024, P=0.382). The tumors in the HBcAg group and the saline group showed incomplete platelet necrosis, and the fusion protein group showed large sheet necrosis with inflammatory cell infiltration. The expression level of EGFRvIII in fusion protein group was significantly lower than that in saline group and HBcAg group (t=3·157, P=0.006; t=2·539, P=0.021). The expression levels of EGFRvIII in the latter two groups were not statistically significant. Difference (t=0.460, P=0.651). CONCLUSION: The PEP-3/HBcAg fusion protein vaccine can induce protective immune responses and has anti-tumor effects.
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