自体DC-CIK细胞治疗晚期肾细胞癌的疗效  

Curative effect of autologous dendritic cell stimulated by cytokine-induced killer cells on metastatic renal carcinoma

作　　者：谭洁[1,2] 王彬[1,2] 何志洁[1,2] 蔡俊霞[1,2] 时建明[1,2] 吴锦昌[1,2] 时宏珍 

机构地区：[1]苏州市肿瘤诊疗中心 [2]南京医科大学附属苏州医院肿瘤内科,江苏苏州215001 [3]南京市免疫细胞生物工程技术研究中心,南京得康生物技术有限公司,江苏南京210019

出　　处：《中国肿瘤生物治疗杂志》2013年第6期711-716,共6页Chinese Journal of Cancer Biotherapy

基　　金：苏州市科技计划资助项目(No.SS0524)~~

摘　　要：目的：探讨自体树突状细胞（dendriticcell，DC）激活的细胞因子诱导的杀伤（cytokine—inducedkiller，CIK）细胞在晚期肾细胞癌（renalcellcarcinoma，RCC）治疗中的临床效果与安全性。方法：采集22例2011年7月至2012年6月期间南京医科大学附属苏州医院肿瘤内科收治的22例RCCIV期患者[男性12例、女性10例，中位年龄60．8岁（21～79岁）]外周血单个核细胞（peripheralbloodmononuclearcell，PBMC），体外制备成DC-CIK细胞。流式细胞术分析DC-CIK细胞中CD3^＋T、CD8^＋T、CD4’T、NK（CD3-CD56^＋）和NKT（CD3^＋CD56^＋）细胞的比例，MTT法检测DC-CIK细胞对白血病K562细胞（对NK细胞敏感）和肾癌786-0细胞（对NK细胞不敏感）的杀伤活性。受试患者于常规治疗（手术＋化疗＋放疗／细胞因子治疗）结束后4周进行DC．CIK细胞治疗，每次静脉回输细胞数约（5．0±0．5）×10。个，5次为1疗程，共3个疗程，分别于疗程开始前与结束后1周内监测患者外周免疫学指标（淋巴亚群、细胞因子谱），严密观察并记录治疗过程中的不良反应。结果：DC-CIK细胞组成为CD3‘细胞占（86．92±5．32）％、CD3^＋CD8^＋CD56^＋（NKT细胞）占（52．04±7．33）％、CD8-CD56^＋（NK细胞）占（7．85±3．15）％，DC-CIK细胞对786-0细胞和K562细胞的体外杀伤率相仿（效靶比为3：1时，杀伤率分别为（16．5±1．7）％和（18．4±1．9）％，P=0．014）。患者接受DC-CIK细胞治疗后，外周血淋巴细胞亚群（CD3^＋T、CD4^＋T、CD8^＋T、CD3CD56^＋NK细胞）比例无显著变化（P〉0．05）；外周血中IL-2、IL-12和IFN-1细胞因子水平较治疗前明显提升（均P〈0．05），而TNF-O／_和IL-10变化不明显（均P〉0．05）。2例患者发生一过性发热，持续4～6h恢复，1例出现短期乏力。结论：DC-CIK细胞体外能有效杀伤786-0细胞和K562细胞。输注后可提升部分RCC患者免疫水平，Objective：To investigate the clinical effect and safety of autologous dendritic cells （DCs） stimulated by cy tokine-induced killer （CIK） cells in patients with advanced renal cell carcinoma （RCC）. Methods： During July 2011 to June 2012, peripheral blood mononuclear cells （PBMCs） were collected from 22 patients （ 12 males and 10 females, me dian age 60.8 years [ 21-79 years] ） with advanced renal carcinoma in the Department of Medical Oncology of Suzhou Hospital affiliated to Nanjing Medical University, and DC-CIK cells were individually prepared from these PBMCs. Flow cytometry was performed to analyz the proportion of CD3 ＋ T, CD8 ＋ T, CIM ^＋ T, NK （ CD3 - CD56 ＋ ） and NKT （ CD3^＋ CD56 ＋ ） cells in the DC-CIK cells. The cytotoxicity of DC-CIK ceils on leukemia K562 cells （ sensitive to NK cells） and renal carcinoma 786-0 cells （insensitive to NK cells） was detected by MTF assay. DC-CIK ceils theranv was started whenthe conventional therapy （ surgery ＋ chemotherapy ＋ radiotherapy/cytokine therapy） finished and continued for 4 weeks. Each time, about （5.0 ± 0.5） x 108 DC-CIK cells were returned through intravenous transfusion, and each patient re- ceived 5 times （one cycle） of DC-CIK cells intravenous infusion. The immunological index such as lymphocyte subsets and cytokine concentration in the peripheral blood were detected before and after DC-CIK infusion. The adverse reactions during the treatment were closely observed and recorded. Results： In the total number of DC-CIK cells, the proportion of CD3 positive （ CD3 ＋ ） lymphocytes was （86.92 ± 5.32） %, while the proportions of CD3 ＋ CD56 ＋ NKT cells and CD3 - CD56 ＋ NK cells were （52.04 ±7.33 ）% and（7.85 ± 3.15）% respectively. DC-CIK cells showed similar in vitro killing ac- tivities on 786-0 cells and K562 cells in vitro, with a killing rate of （16.5 ± 1.7 ） % and （18.4 ± 1.9） % respeetively （P = 0. 014）, when the ratio of effeet cells and target cell

关 键 词：自体DC-CIK细胞 肾细胞癌 免疫治疗 

分 类 号：R737.11[医药卫生—肿瘤] R730.51[医药卫生—临床医学]