树突状细胞和脑胶质瘤自体免疫治疗的实验和临床研究(英文)

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 诱导细咆毒性 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,术后仪接受放疗。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。

Experimental and Clinical Research of Dendritic Cell and Syngeneic Immunotherapy of Brain Glioma

Objective:To investigate the clinical effect and prospective use of syngeneic brain glioma antigen dendritic cell(DC)vaccine.Methods:DCs were isolated from peripheral blood of brain glioma patients. DCs loaded with different tumor antigens were cocultured with T lymphocytes.The cytotoxity of T lymphocytes to glioma cells was tested by LDH method.Fifty-six glioma patients were divided into 3 groups treated with different methods.Experimental group(19 cases):syngeneic brain glioma antigen DC vaccine and bacilie calmette guerin(BCG);Positive control group(17 cases):glioma homogenate and BCG: Negative control group(20 cases):only radiotherapy after resection.Therapeutic effect of every group was evaluated.Results:High purity DCs could be harvested by GM-CSF and IL-4 culture.The cytotoxicity of DC was enhanced when loaded with tumor antigen.There were different therapeutic effects among 3 groups.The median survival time in group 1(38 months)and group 2(24 months)was significantly longer than that in group 3(13 months).Conclusion:Syngeneic brain glioma antigen DC vaccine could inhibit the recurrence and progression of glioma.This method can prolong the survival time of brain glioma patients.