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目的 对树突状细胞(DC)肿瘤疫苗进行实验和临床研究并探讨其应用前景。方法 从脑胶质瘤患者外周血提取DC进行培养并对其进行形态学和免疫学鉴定。采用乳酸脱氢酶(LDH)释放法检测负载不同肿瘤抗原的DC诱导细胞毒性T细胞(CTL)体外杀伤活性。在实验研究的基础上拟定临床治疗方案:将56例脑胶质瘤术后患者分为3组,实验组19人接受冻融法制备的自体肿瘤抗原DC疫苗和卡介苗(BCG)治疗,阳性对照组17人接受全肿瘤组织匀浆和BCG治疗,阴性对照组20人,术后仅接受放疗。结果 采用粒细胞、巨噬细胞集落刺激因子(GM-CSF)及白细胞介素-4(IL-4)培养可获得高纯度的DC。DC在负载肿瘤抗原后诱导CTL杀伤活性大大提高而DC与肿瘤细胞共培养对CTL杀伤活性无显著影响。临床治疗中实验组中位数生存时间大于38个月,阳性对照组为24个月,二者均高于阴性对照组(13个月)。生存分析示3组间的生存曲线分布差异有显著性意义。结论 采用冻融法制备的自体脑胶质瘤抗原DC疫苗可抑制脑胶质瘤的复发和进展,从而有效地延长脑胶质瘤患者的生存时间,有良好的临床应用前景。
Objective To study the experimental and clinical study of dendritic cell (DC) tumor vaccine and to explore its application prospects. Methods DCs from peripheral blood of patients with glioma were cultured and identified by morphology and immunology. In vitro killing activity of cytotoxic T lymphocytes (CTLs) induced by DC loaded with different tumor antigens was detected by lactate dehydrogenase (LDH) release assay. On the basis of experimental study, the clinical treatment plan was drawn up: 56 cases of glioma postoperative patients were divided into 3 groups, 19 cases of experimental group received autologous tumor antigen DC vaccine and BCG prepared by freeze-thaw method, positive control Group 17 received total tumor homogenate and BCG treatment, negative control group of 20 patients received only postoperative radiotherapy. Results High purity DCs were obtained using GM-CSF and IL-4. DCs induced CTL cytotoxicity significantly after loading tumor antigen while DC co-cultured with tumor cells had no significant effect on CTL cytotoxicity. The median survival time of the experimental group was more than 38 months in the clinical trial and 24 months in the positive control group, both of which were higher than the negative control group (13 months). Survival analysis showed significant differences in the distribution of survival curves among the three groups. Conclusion The DC glioma vaccine prepared by freeze-thaw method can inhibit the recurrence and progression of glioma, which can effectively prolong the survival time of patients with glioma and has a good clinical application prospect.