DC疫苗联合CIK细胞治疗非小细胞肺癌疗效观察

目的探讨自体肿瘤抗原负载的树突状细胞（DC）联合细胞因子诱导的杀伤细胞（CIK）在非小细胞肺癌治疗中的临床疗效.方法采集70例非小细胞肺癌患者外周血单个核细胞,加入细胞因子定向诱导成CIK及DC,培养的第5天用自体肿瘤抗原（Ag）负载DC,第8天将DC与CIK细胞共培养,14d后将联合培养的细胞（Ag-DC-CIK）分次回输给患者.治疗4周后,流式细胞仪检测患者外周血T细胞亚群及细胞因子水平,以评价细胞免疫功能,结合临床指标综合评价疗效,同时观察不良反应;以35例单纯的CIK细胞治疗作为对照.结果（1）培养的第14天,Ag-DC-CIK细胞的增殖达（20.6±2.16）倍,对照组仅为（12.2±2.65）倍（P〈0.05）;CD3＋CD8＋细胞及CD3＋CD56＋细胞的表达也明显高于对照组（P〈0.05）;（2）70例接受治疗的患者中CD3、CD4、CD8T细胞的百分比均较治疗前有不同程度的提高,Ag-DC-CIK组57.14%（20例）的患者CD4/CD8比例调节至正常,与对照组（42.85%,15例）相比差异有统计学意义（P〈0.05）;（3）Ag-DC-CIK治疗后51.42%（18例）的患者Thl/Th2细胞因子比例恢复正常,而对照组恢复正常者仅占37.14%（13例）（P〈0.05）;（4）Ag-DC-CIK治疗组中Ⅱ、Ⅲ期患者的有效率分别为39.30%和28.60%,与对照组的相应期别（Ⅱ期26.90%,Ⅲ期22.20%）相比差异有统计学意义（P〈0.05）;（5）治疗后的副反应包括寒颤、发热及兴奋失眠,无1例出现毛细血管渗漏综合征及实质脏器的损害.结论肿瘤抗原负载的DC细胞可增强CIK细胞在非小细胞肺癌治疗中的临床疗效,有推广运用的价值.

The Effects of DCs Vaccine Combined with CIK Cells on Non-small Cell Lung Cancer

Objective To explore the effects of autologous tumor antigen-loaded DCs combined with CIK cells on non-small cell lung cancer.Methods Peripheral blood mononuclear cells of 70 patients were separated and cultured in medium with different cytokines to be induced into CIKs and DCs.In day 5,DCs were loaded with autologous tumor antigen（Ag） and co-cultured with CIKs in day 8.14 days later,Ag-DC-CIK cells were transfused back to the patients.Lymphocyte subsets and cytokine production were determined by flowcytometry after 4 weeks,which reflecting the immune function of patients.At the same time,other clinical items were combined to evaluate the comprehensive curative effects and adverse reactions.Pure CIK cells therapy was used ascontrol.Results（1） Compared with control,Ag-DC-CIK group got a significant increase of proliferation in day 14 （20.6 ±2.65） times vs（12.2 ±2.65） times,P 0.05] and so of the expression rate of CD3＋CD8＋,CD3＋CD56＋cells（P 0.05）.（2） The expression rate of CD3,CD4,CD8 T cell subsets of 70 patients were increased in different degrees.The CD4/ CD8 proportion of 57.14%（20 Cases） patients in Ag-DC-CIK group was adjusted into normal state,but only 42.85%（15caes） in control group（P0.05）.（3） The cytokines secreting by Th1/Th2 T cells of 51.42%（18cases） patients regained balance,significant higher than the control 37.14%（13cases）（P0.05）.（4） Compared with control,Ag-DC-CIK got a higher effective rate in different stages （39.30% vs 26.90% in stageⅡ） and（28.60% vs 22.20% in stageⅢ） P0.05].（5） Side effects included rigor,fever,excitation and insomnia.No blood capillary leakage syndrome and visceral damage were observed in all patients.Conclusion Tumor antigen-loaded DCs can improve the clinical effects of CIKs against non-small cell Lung cancer,and so the co-culture is a method worth promoting.