以链球菌制剂OK432为佐剂的内皮细胞疫苗体内抗小鼠肝癌转移的作用（英文）

发布时间：2018-05-23 13:51

本文选题：疫苗 + 脐静脉内皮细胞　；参考：《中国药理学与毒理学杂志》2015年01期

【摘要】：目的评估OK432作为佐剂制备的内皮细胞疫苗体内抗肿瘤转移的作用。方法以OK432为佐剂,体外混合人脐静脉内皮细胞(HUVEC),制备HUVEC-OK432疫苗。雄性健康BALB/c小鼠尾静脉注射肝癌细胞5×105建立肝癌肺转移模型,皮下注射HUVEC-OK432疫苗,分别在预防性和治疗性免疫中评价HUVEC-OK432疫苗抗肿瘤转移活性;皮内注射5×104肝癌细胞建立皮内肿瘤血管模型,皮下注射HUVEC-OK432疫苗,评价HUVEC-OK432疫苗抑制肿瘤新生血管的活性;采用ELISA的方法测定小鼠免疫血清中HUVEC抗体水平;采用细胞毒T淋巴细胞(CTL)实验考察HUVEC-OK432疫苗诱导的细胞免疫应答水平。结果肺转移模型结果显示,在预防性和治疗性免疫中,HUVEC-OK432免疫均能有效降低小鼠肺上的肿瘤转移灶数目(P0.01);皮内肿瘤血管模型的结果显示,HUVEC-OK432免疫能显著降低肿瘤新生血管的数目(116.5±20.6 vs 45.0±8.9,P0.01);ELISA测定抗体的结果显示,HUVEC-OK432初次免疫后1周小鼠即产生了高滴度的特异性HUVEC抗体,随免疫次数的增加抗体水平不断升高,且该抗体在体外可以显著抑制HUVEC细胞的增殖;CTL实验的结果表明,HUVEC-OK432免疫组淋巴细胞体外有明显的特异性杀伤HUVEC的作用。结论 HUVEC-OK432疫苗免疫可以有效诱导小鼠产生靶向内皮细胞的免疫应答,从而有效抑制小鼠肝癌细胞转移。
[Abstract]:Objective to evaluate the anti-tumor effect of endothelial cell vaccine (ECV) prepared by OK432 as adjuvant in vivo. Methods Human umbilical vein endothelial cells (HUVECs) were mixed with OK432 as adjuvant in vitro to prepare HUVEC-OK432 vaccine. The lung metastasis model of liver cancer was established by injecting 5 脳 10 ~ 5 liver cancer cells into male healthy BALB/c mice. The antitumor activity of HUVEC-OK432 vaccine was evaluated in prophylactic and therapeutic immunizations by subcutaneous injection of HUVEC-OK432 vaccine. Intradermal tumor vascular model was established by intradermal injection of 5 脳 10 ~ 4 hepatoma cells, and HUVEC-OK432 vaccine was injected subcutaneously to evaluate the inhibitory effect of HUVEC-OK432 vaccine on tumor neovascularization. ELISA method was used to determine the level of HUVEC antibody in mouse immune serum. The level of cellular immune response induced by HUVEC-OK432 vaccine was investigated by cytotoxic T lymphocyte assay. Results the lung metastasis model showed that, Both prophylactic and therapeutic immunizations with HUVEC-OK432 could effectively reduce the number of tumor metastasis foci in the lung of mice and the results of intradermal tumor vascular model showed that HUVEC-OK432 immunized tumor neovascularization significantly decreased the number of tumor neovascularization (116.5 卤20.6 vs 45.0 卤8.9P0.01ELISA) and the results showed that HUVEC-OK432 could significantly reduce the number of tumor neovascularization vessels (116.5 卤20.6 vs 45.0 卤8.9 P0.01 Elisa). The results showed that a high titer of specific HUVEC antibody was produced in HUVEC-OK432 mice one week after the first immunization. The antibody level increased with the increase of immunization times, and it could significantly inhibit the proliferation of HUVEC cells in vitro. The results showed that the lymphocytes of HUVEC-OK432 immunized group had a specific killing effect on HUVEC in vitro. Conclusion HUVEC-OK432 vaccine can effectively induce the immune response of mice to target endothelial cells, thus effectively inhibit the metastasis of mouse hepatoma cells.
【作者单位】：滨州医学院药学院;滨州医学院基础医学院;
【基金】：supported by Shandong Provincial Natural Science Foundation of China(ZR2013BM022);Shandong Provincial Natural Science Foundation of China(ZR2013EMQ008) Promotive Research Fund for Excellent Young and Middle-aged Scientisits of Shandong Province(BS2014YY051) Medicine and Health Science Technology Plan of Shandong Province(2014WS0479) Science and Technology Development Plan of Yantai City(2013ZH095);Science and Technology Development Plan of Yantai City(2013ZH097)~~
【分类号】：R965

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