针对HER-2的多肽疫苗CKL9与YL20的抗肿瘤活性研究

发布时间：2018-02-09 21:50

本文关键词： HER- 多肽疫苗 T淋巴细胞免疫应答 N移植瘤抗肿瘤活性　出处：《中国药理学通报》2017年07期 　论文类型：期刊论文

【摘要】：目的研究能够诱导激活细胞免疫应答的多肽疫苗CKL9、YL20在细胞水平和整体动物水平的抗HER-2阳性肿瘤作用,为肿瘤新药开发提供依据。方法采用CCK-8法检测CKL9、YL20诱导小鼠淋巴细胞的增殖作用,采用LDH法检测细胞毒性T淋巴细胞(CTL)的活性,采用动物体内实验评价CKL9、YL20的抗肿瘤活性。结果 CCK-8检测淋巴细胞增殖实验表明体外孵育多肽CKL9、YL20在一定程度上能够促进淋巴细胞增殖,在50 mg·L~(-1)孵育浓度下,CKL9、YL20相对增殖率分别为11.1%、16.7%;LDH法检测细胞毒性实验表明经多肽疫苗CKL9、YL20诱导分化的T淋巴细胞对HER-2阳性的肿瘤细胞有杀伤作用,当效靶比为80∶1时,细胞毒性T淋巴细胞对肿瘤细胞抑制率分别可达89.8%和84.3%;动物体内实验表明预免疫多肽CKL9、YL20能对BALC/c小鼠N87移植瘤产生明显抑制作用。结论基于HER-2的多肽疫苗CKL9、YL20具有免疫原性,可诱导特异性CD4和CD8 T淋巴细胞免疫,以抑制HER-2阳性肿瘤细胞生长。
[Abstract]:Objective to study the anti-tumor effect of polypeptide vaccine CKL9 / YL20, which can induce cellular immune response, against HER-2 positive tumor at the cell level and the animal level as a whole. Methods CCK-8 assay was used to detect the proliferation of murine lymphocytes induced by CKL9, and the activity of cytotoxic T lymphocytes was detected by LDH assay. The antitumor activity of CKL9 / YL20 was evaluated by animal experiments in vivo. Results CCK-8 assay showed that in vitro incubation of CKL9 / YL20 could promote the proliferation of lymphocytes. The relative proliferative rate of CKL9 / YL20 was 11.1mg 路L ~ (-1) at 50 mg 路L ~ (-1). The cytotoxicity test showed that the differentiated T lymphocytes induced by polypeptide vaccine CKL9 / YL20 could kill HER-2 positive tumor cells, and when the effective / target ratio was 80: 1, the cytotoxicity of T lymphocytes induced by polypeptide vaccine CKL9 / YL20 was 80: 1. The inhibitory rates of cytotoxic T lymphocytes on tumor cells were 89.8% and 84.3, respectively, and in vivo experiments showed that CKL9 and YL20, a preimmunized polypeptide, could significantly inhibit N87 transplanted tumor in BALC/c mice. Conclusion the peptide vaccine CKL9 / YL20 based on HER-2 has immunogenicity. It can induce specific CD4 and CD8 T lymphocyte immunity to inhibit the growth of HER-2 positive tumor cells.
【作者单位】：暨南大学生命科学技术学院基因工程药物国家工程研究中心;广州领晟医疗科技有限公司;
【基金】：广东省科技计划项目(No 2015A020211016)
【分类号】：R392-33

【相似文献】