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。
Aim To explore whether the polypeptide vaccines CKL9 and YL20 can induce immune response and anti-tumor effect on HER-2（＋） tumors in vitro and in vivo,and to provide suggestions for clinical use.Methods The proliferation of specific lymphocytes and cytotoxic T lymphocyte activity（CTL） stimulated by CKL9 and YL20 were studied with CCK-8 assay and LDH assay,and the antitumor activity of CKL9 and YL20 was evaluated in vivo.Results The lymphocyte proliferation was promoted by incubation with CKL9 and YL20,and the relative increase of cells was11.1% and 16.7% respectively at the concentration of50 mg·L^-1of CKL9 and YL20.The LDH assay confirmed the CTL effect induced by CKL9 and YL20 onHER2-positive tumor cells,not on HER2-negtive tumor cells.With an effector-target ratio of 80 ∶ 1,the inhibition of tumor cell by cytotoxic T lymphocyte stimulated by CKL9 and YL20 could reach 89.8% and84.3%,respectively.The HER2（＋） tumor cell N87 transplanted in Babes mice was inhibited by pre-immune polypeptide CKL9 and YL20.Conclusion The HER2-specific polypeptide vaccines CKL9 and YL20 could induce persistent specific CD4 and CD8 T cell immune and inhibit the growth of HER2 positive tumor cells.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第7期997-1002,共6页
Chinese Pharmacological Bulletin
基金
广东省科技计划项目(No 2015A020211016)
