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目的探讨重组非洲爪蟾血管内皮细胞生长因子(Xenopuslaevisvascularendothelialgrowthfactor,xVEGF)肿瘤疫苗免疫治疗,联合阿霉素抗小鼠淋巴瘤的作用。方法采用C57BL/6小鼠建立EL4淋巴瘤模型。实验小鼠随机分成4组xVEGF联合阿霉素组(简称联合用药组)、阿霉素组、xVEGF组、生理盐水对照组。观察肿瘤生长、小鼠生存率和毒副反应,并检测分泌抗自身VEGF抗体的B细胞、肿瘤微血管密度(microvesseldensity,MVD)和肿瘤细胞凋亡等。结果联合用药组肿瘤明显小于其他3组(P<0.05),其中有3只小鼠肿瘤完全消退;接种肿瘤后48d,联合用药组小鼠生存率为100%,明显高于生理盐水对照组(0%)(P<0.01)。ELISPOT检测发现,异种蛋白质疫苗免疫的小鼠(联合或单用)产生了分泌抗自身VEGF抗体的B细胞,其数量与阿霉素组或生理盐水对照组相比差异有统计学意义(P<0.01)。联合用药组肿瘤MVD明显低于其他3组(P<0.05),肿瘤细胞凋亡指数明显高于其他3组(P<0.05)。结论采用异种同源蛋白质疫苗xVEGF免疫治疗,与阿霉素化疗联合有协同增强的抗小鼠淋巴瘤的作用。
Objective To investigate the immunotherapy of Xenograft Xenograft Xenograft Growth Factor (Xenovirus) Xenograft Xenograft Growth Factor (xVEGF) tumor vaccine in combination with doxorubicin against mouse lymphoma. Methods C57BL / 6 mice were used to establish EL4 lymphoma model. The experimental mice were randomly divided into 4 groups of xVEGF combined with doxorubicin (referred to as combination therapy group), doxorubicin group, xVEGF group, saline control group. Tumor growth, survival rate and toxicity were observed. B cells secreting anti-VEGF antibody, microvessel density (MVD) and apoptosis of tumor cells were also detected. Results Compared with the other three groups, the tumors in the combination group were significantly less than those in the other three groups (P <0.05), and the tumors in three of the three groups completely regressed. At 48 d after the tumor inoculation, the survival rate was 100% in the combination group, significantly higher than that in the saline control group 0%) (P <0.01). The ELISPOT assay showed that mice immunized with the heterologous protein vaccine (either alone or in combination) produced B cells that secrete anti-VEGF antibodies, which was statistically different from that of the doxorubicin group or saline control group (P < 0.01). MVD in the combination group was significantly lower than the other three groups (P <0.05), and the apoptosis index was significantly higher in the combination group than in the other three groups (P <0.05). Conclusion The xenogenic protein vaccine xVEGF immunotherapy combined with doxorubicin chemotherapy has a synergistic anti-mouse lymphoma effect.