负载人热休克蛋白抗原肽的树突状细胞瘤苗在诱导抗胃癌免疫效应中的作用

The Immunological Effect of Dendritic Cells Loaded with Autologous Tumor-Derived Heat-Shock Protein Vaccine against Gastric Cancer

目的评价负载人热休克蛋白70抗原肽的树突状细胞(HSP70PCs-DC)瘤苗在胃癌个体化治疗中引发的免疫应答。方法提取15例胃癌患者术后肿瘤组织的HSP70,其中5μg负载DC回输8例患者(5μg组)和50μg回输7例患者(50μg组),并分别在治疗前及第1次接种后的第6,9,13,17周采集抗凝外周血5mL,采用ELIS-POT技术检测抗原特异性T细胞数量,评价该瘤苗能否诱导抗胃癌的免疫应答。结果 11例(73.33%)患者在接受第一个疗程治疗后的第2周斑点数出现显著变化,9例在第9,13周时斑点数达到高峰,有效率81.82%(9/11),其后缓慢下降,但在第17周仍高于治疗前(P=0.001);从剂量上看,5μg组在各时间点平均每位患者的应答斑点数均高于50μg组,差别有统计学意义(P=0.008);未发生严重不良事件。结论 HSP70PCs-DC瘤苗具有较强的诱导患者抗肿瘤的细胞免疫应答功能,主要效应细胞是CD8+T细胞和Th1型细胞。该疫苗为抗肿瘤疫苗的进一步研究打下基础。

Objective To evaluate the immune response of dendritic cells loaded with autologous heat-shock protein 70 vaccination against gastric cancer by the ELISPOT assay.Methods HSP70 peptide complex was isolated from the fresh samples of 15 patients undergoing radical gastric cancer resection,and then was used to pulse the dendritic cells as the vaccination.The ELISPOT assay for interferon-γ production has been used to analyze specific T cell responses which were performed on peripheral blood mononuclear cells（PBMC）,before the first immunization and 6 weeks,9 weeks,13 weeks and 17 weeks after vaccination.Results Two weeks after the first course of treatment,11（73.3%） of the 15 patients displayed a significant increase in the number of IFN-γ spot,and it reached a peak at the 9th week and the 13th week,then it declined slowly but still had a statistically significant increase（P=0.001）at the 17th week.The 5 μg dose can caused the higher mean spot number of antitumor immune reactions than 50 μg（P=0.008） at different time point.No relevant toxicity was observed.Conclusion HSP70PCs-DC vaccination after resection of gastric cancer induced cancer-specific immune responses,including CD8＋ T cells and Th1 cells.The vaccination could form a basis for future trails with clinical research.