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目的检测基于人端粒酶逆转录酶(human telomerase reverse transcriptase,hTERT)细胞毒性T淋巴细胞(cytotoxic T lymphocyte,CTL)表位R540的多抗原肽(multiple antigen peptide,MAP)的体外抗肿瘤活性。方法将HLA-A2限制性hTERT CTL表位的多抗原肽负载正常人外周血来源(peripheral blood mononuclear cell,PBMC)的树突细胞,并将负载多肽的树突细胞刺激淋巴细胞产生hTERT特异性的CTL细胞,采用51Cr释放实验检测所诱导的CTL细胞体外抗肿瘤杀伤效应。结果 hTERT特异性CTL表位的多抗原肽所诱导的CTL细胞对hTERT及HLA-A2表达均阳性的肿瘤细胞杀伤作用较之其单肽疫苗杀伤活性明显增强,在最大效靶比(E/T)80∶1时,高出率均大于25%。而对HLA-A2阴性的HepG2肝癌细胞及hTERT阴性的U2OS骨肉瘤细胞不具有杀伤效应,同时其对自体淋巴细胞和树突细胞也不具有杀伤效应。结论 HLA-A2限制性hTERT CTL表位多抗原肽相较于其单肽能在体外诱导更强的抗肿瘤免疫效应。
Objective To detect the antitumor activity of multiple antigen peptide (MAP) based on the R540 epitope of human telomerase reverse transcriptase (hTERT) cytotoxic T lymphocyte (CTL). Methods Multi-antigen peptides of HLA-A2-restricted hTERT CTL epitopes were loaded on dendritic cells of normal peripheral blood mononuclear cells (PBMCs) and loaded with peptide-dendritic cells to stimulate lymphocytes to produce hTERT-specific CTL cells, 51Cr release assay was used to detect the induced CTL cells in vitro anti-tumor effect. Results The cytotoxicity of CTL cells induced by multi-antigen peptide of hTERT-specific CTL epitopes to tumor cells positive for both hTERT and HLA-A2 was significantly enhanced compared with that of single peptide vaccine. The maximum effective target ratio (E / T ) 80: 1, the high rate of more than 25%. However, it does not have killing effect on HLA-A2 negative HepG2 hepatocarcinoma cells and hTERT negative U2OS osteosarcoma cells, and it also has no killing effect on autologous lymphocytes and dendritic cells. Conclusion HLA-A2-restricted hTERT CTL epitopes can induce stronger antitumor immunity in vitro compared with their single peptides.