自体热休克凋亡细胞负载树突状细胞治疗大肠癌的疗效观察  

Vaccination with apoptosis colorectal cancer cell pulsed autologous dendritic cells in advanced colorectal cancer patients

作　　者：金成[1] 鲍传庆[1] 许炳华[1] 沈晓明[1] 张淳[1] 陆晓[1] 

机构地区：[1]无锡市第三人民医院胃肠外科,江苏无锡214041

出　　处：《现代肿瘤医学》2011年第4期718-721,共4页Journal of Modern Oncology

基　　金：2009年无锡三院青年基金资助项目;科研人才资助项目(编号:SYQNJJ09004)

摘　　要：目的:探讨自体热休克凋亡细胞负载的树突状细胞(dendritic cells,DC)治疗大肠癌的临床疗效。方法:采用酶消化法从手术切除的14例大肠癌新鲜组织获得单细胞悬液,热休克处理后用桦脂酸诱导其凋亡制备成细胞抗原;采集外周静脉血,分离单个核细胞,经GM-CSF与IL-4体外诱导成未成熟树突状细胞,负载细胞抗原后制备成DC肿瘤疫苗;对14例大肠癌患者进行4个疗程的DC免疫治疗,观察患者不良反应、敏感程度、生存质量、生存时间、癌胚抗原等临床指标。结果:DC治疗大肠癌未出现明显不良反应,5例患者的DTH检测阳性;14例患者的平均CEA水平由治疗前的99.5ng/ml降至治疗后的71.4ng/ml(P<0.05);治疗后血清中IL-2、IL-12及IFN-γ浓度均显著高于治疗前,具有统计学差异(P<0.05);所有患者均生存1年,其中1例患者出现了短暂的后腹膜淋巴结缩小,持续3个月,第2年由于肿瘤的进展生存率下降,由80%降至20%;患者的KPS评分上升,与治疗前比较有所改善(P<0.05)。结论:自体热休克凋亡细胞负载的DC治疗大肠癌在临床治疗中具较高安全性,可改善患者免疫功能,临床观察显示患者近期临床效果明显;为大肠癌的临床综合治疗提供了一种新方法。Objective：To study vaccination with apoptosis colorectal cancer cell pulsed autologous DCs in advanced colorectal cancer（CRC） patients.Methods：Dendritic cells（DCs）isolated from peripheral blood mononuclear cell of the patients with advanced colorectal cancer（CRC） were cultured and proliferated in vitro by using rhGM-CSF and rhIL-4,and then were loaded with heat shock-induced apoptotic colorectal cancer cell.In this study,14 patients with advanced CRC were enrolled and treated with DCs vaccine to assess toxicity,tolerability and clinical responses to the vaccine.Results：No severe toxicity was observed and the vaccine was well tolerated.The levels of IL-2,IL-12 and IFN-γ significantly increased after DCs vaccination（P0.05）.Mean of CEA lever decreased from 99.5ng/ml to 71.4ng/ml.Five patients showed a positive skin response to the apoptotic cells loaded DCs vaccines in the delayed type hypersensitivity（DTH）.During the two years of clinical observation,all of patients survived in the first year,we found a patient with a lymphoglandulae coeliacae metastasis;temporary seroperitoneum regression was demonstrated by CT scan.While the survival rate decreased from 80% to 20% during the second year.The KPS score was improved significantly after treatment（P0.05）.Conclusion：In conclusion,the strategy for vaccination of apoptosis colorectal cancer cell pulsed-DCs may raise the clinical response of CRC patients.

关 键 词：大肠癌 树突状细胞 免疫治疗 

分 类 号：R735.34[医药卫生—肿瘤]