异种VEGF疫苗免疫治疗联合化疗抗实体瘤的实验研究  

Antitumor effects of immunotherapy with xenogeneic VEGF vaccine combined with chemotherapy on solid tumor in mice

作　　者：牛挺[1] 刘霆[1] 贾永前[1] 刘继彦[1] 吴扬[1] 胡兵[1] 田聆[1] 杨莉[1] 阚兵[1] 魏于全[1] 

机构地区：[1]四川大学华西医院生物治疗国家重点实验室

出　　处：《免疫学杂志》2005年第5期351-354,共4页Immunological Journal

基　　金：国家重点基础研究发展计划(973计划)项目(2004CB518807);科技部基础研究重大项目前期研究专项(国科基字[2001]50号)资助

摘　　要：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,联合小剂量阿霉素化疗抗小鼠纤维肉瘤的作用。方法实验小鼠随机分成4组xVEGF联合阿霉素组(简称联合用药组)、单用阿霉素组、单用xVEGF组、生理盐水对照组。观察各组肿瘤生长、小鼠生存率和毒副反应,并检测抗自身VEGF抗体、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单用阿霉素组和单用xVEGF组(P<0.05),或生理盐水对照组(P<0.01),联合用药组有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%,明显高于单用阿霉素组和单用xVEGF组生存率(P<0.05),或生理盐水对照组(P<0.01)。WesternBlot和ELISPOT检测发现,联合组或单用xVEGF组小鼠产生了抗自身VEGF抗体,其分泌抗自身VEGF抗体的B细胞数量,与阿霉素组或生理盐水对照组相比,有显著性差异(P<0.01)。联合用药组肿瘤MVD减少和细胞凋亡指数升高与三个对照组比较有显著性差异(P<0.05)。结论异种同源蛋白质疫苗xVEGF与小剂量阿霉素联合治疗有协同增强的抗小鼠实体瘤的作用。Objective To explore antitumor effects of immunotherapy with recombinant Xenopus laevis vascular endothehal growth factor （xVEGF） as a vaccine combined with low-dose adriamycin in Meth A fibrosarcoma model in mice. Methods Mice were randomized into four groups： combination therapy, adriamycin alone, xVEGF alone, and normal saline （NS） groups. Tumor growth, survival rate of tumorbearing mice, and potential toxicity of regimens above were observed. Anti-VEGF antibodies and anti-VEGF antibody-producing B cells （APBCs） were detected by Western blot analysis and enzyme-linked immunospot （ELISPOT） assay, respectively. In addition, microvessel density （MVD） of tumor and tumor cell apoptosis were detected by immunohistochemistry and TUNEL staining, respectively. Results Tumor volumes of mice in combination group were significantly smaller than those in adriamycin alone group, in xVEGF alone group （P〈0.05）, or in NS group （P〈0.01）. Complete regression of tumor was observed in 3 of 10 mice in combination group. Forty-eight days after inoculation of tumor cells, survival rate of mice was significantly higher in combination group than that in adriamycin alone group, in xVEGF alone group （P〈0.05）, or in NS group （P〈0.01）. Anti-VEGF antibodies were found by Western blot analysis in mice treated with xVEGF （combination or xVEGF alone group）, and anti-VEGF APBCs counts in these two groups were significantly higher compared with adriamycin alone or NS group （ P〈0.01 ）. Significant difference was found between combination group and other three groups in terms of MVD in tumor tissues and tumor cell apoptosis （P〈0.05）. Conclusion The combination therapy of xVEGF and low-dose adriamycin induces synergistic antitumor effect on solid tumor in mice.

关 键 词：血管内皮细胞生长因子 阿霉素 实体瘤 免疫治疗 化学治疗 

分 类 号：R73-3[医药卫生—肿瘤]