CEA多肽致敏的树突状细胞(DC)治疗晚期非小细胞肺癌临床初步研究

A primary study of immunotherapy with carcinoembryonic antigen peptide-pulsed, autologous human cultured dendritic cells in patients with advanced non-small cell lung cancer

背景与目的树突状细胞（DC）为基础的免疫治疗是肿瘤治疗的新领域，对部分恶性肿瘤有较好的疗效。本研究的目的是应用癌胚抗原（CEA）致敏的DC治疗晚期非小细胞肺癌（NSCLC），观察其临床应用方法、毒副反应和剂量效应。方法选择CEA高表达的肺癌患者，体外培养外周血单个核细胞来源的DC及CIK，CEA多肽于培养的第5天加入培养液以致敏未成熟DC。将DC和CIK细胞静脉回输患者，观察回输后的疗效和毒副反应。结果共22例晚期NSCLC患者接受了DC治疗。回输DC数量为2．5×10^6～9．6×10^7，平均5．03×10^6；回输CIK细胞数量为3．4×10^8～46×10^8。治疗后CD3、CD8、NK、IFN-γ明显升高（P〈0．05）。全组1年生存率为68．2％（15／22）。主要毒副反应为发热和皮疹。结论DC生物免疫治疗具有较好的耐受性和安全性。

Background and objective Dendritic cell （DC）-based immunotherapy is a new approach and effective for some malignant tumors. The aim of this study is to observe the efficacy and toxicity of immunotherapy with carcinoembryonic antigen （CEA） peptide-pulsed DCs in patients with refractory advanced lung cancer. Methods Lung cancer patients with high CEA expression were enrolled into this project. Autologous DCs were generated from patients＇ plastic-adherent peripheral blood mononuclear cells and loaded with CEA 5 days later. Cytokine-induced killer cells （CIK） were cultured from non-adherent peripheral blood mononuclear cells. DCs and CIK were transfused to patients. Responses and toxicities were observed. Results A total of 22 patients with lung cancer received DCs immunotherapy. DCs doses were 2.5×10^6～9.6×10^7,（5.03×10^6）. CIK doses were 3.4×10^8～46×10^8. CD3, CD8, NK and IFN-γ levels obviously increased after treatment （P d0.05）. The 1-year survival rate was 68.2% （15/22）. Main toxicities were fever and rash. Conclusion DCs-based immunotherapy is feasible and safe to patients with lung cancer.