乳腺癌细胞抗原肽修饰树突状细胞的抗肿瘤作用  

An in vitro and in vivo study on the antitumor effect of DC vaccine modified by peptide complexes from breast cancer cells

作　　者：汪谢丹[1] 郑启昌[1] 宋自芳[1] 尚丹[1] 屈新才[1] 

机构地区：[1]华中科技大学同济医院附属协和医院普外科,武汉430022

出　　处：《中华普通外科杂志》2007年第3期222-225,共4页Chinese Journal of General Surgery

摘　　要：目的 探讨经重组乳腺癌热休克蛋白70（heat shock protein 70，HSP70）抗原肽复合物修饰后的树突状细胞（dendritic cell，DC）的抗肿瘤作用。方法 冻融法获取BALB／C小鼠4T1乳腺癌细胞抗原肽，体外重组HSPT0-4T1抗原肽复合物。检测BALB／C小鼠DC经该复合物修饰成熟后IL-12和TNFa的分泌。检测修饰后成熟的DC对BALB／C小鼠脾淋巴细胞的增殖作用及增殖后淋巴细胞对4T1细胞的杀伤功能。BALB／C小鼠注射修饰成熟DC，观察该方法对4T1乳腺癌株的抑制作用。结果0．75μg抗原肽与HSP70结合，可使1×10^6DC成熟；成熟后的5×10^3DC可激活2×10^6小鼠脾淋巴细胞。与直接用HSPT0-4T1复合物刺激脾细胞比较，DC途径抗原肽的用量减少40倍。增殖后淋巴细胞对4T1细胞杀伤率为（60．24±6．23）％。接种该DC能有效地抑制肿瘤的生长。结论 重组乳腺癌热休克蛋白70-抗原肽复合物能够诱导DC成熟，成熟后的DC能激活淋巴细胞并抑制肿瘤生长。该途径能有效降低肿瘤免疫治疗时抗原肽的使用剂量。Objective To investigate the in vitro and in vivo antitumor effect of dendritic cell （DC） modified by reconstruct HSP70-tumor peptide complexes. Methods The tumor antigen peptides from 4T1 breast cancer cells were acquired by freeze thawing method and HSP70-4T1 peptides complex was reconstructed in vitro. The levels of IL-12 and TNFa secreted by DC of BALB/C mouse modified by HSP70- 4T1 peptides complex was detected. The activation of lymphocytes by modified DC and the cytotoxicity of the activated lymphocytes to 4T1 cell were tested in vitro. The inhibition for 4T1 tumor in BALB/C mouse by injection of modified DC was observed in vivo. Results 0. 75 ttg of 4T1 peptide bounded to HSP70 could mature 1 × 10^6 DC. 5 × 10^3 modified DC could activate 2 × 10^6 lymphocytes. The dose of peptides could be reduced to 1/40 if the modified DC was used to substitute for direct use of HSP70-4T1 peptides complex stimulated for the same amount of lymphocyte. The activated lymphocytes could specifically kill 4T1 cells in vitro, the kill rate was （60. 24 ± 6. 23 ）%. 4T1 tumor growth in BALB/C mouse could be inhibited significantly by injection DC modified by HSP70-4T1 peptide complexes. Conclusion HSP70-4T1 peptide complexes could effectively modify DC from BALB/C mouse; these modified DC can specifically activate lymphocytes and effectively inhibit 4T1 tumor growth in BALB/C mouse. The dose of peptides could be reduced significantly by DC presenting to activated lymphocytes.

关 键 词：乳腺肿瘤 树突细胞 热休克蛋白70 肿瘤免疫 

分 类 号：R686[医药卫生—骨科学]