自体肿瘤抗原致敏的树突状细胞联合细胞因子诱导杀伤细胞应用于肺腺癌治疗的临床研究  

Autologous tumor antibody-pulsed dendritic cells combined with cytokine-induced killer cells in the clinical treatment of lung adenocarcinoma

作　　者：钟国成[1] 张小玉[2] 孙薏[1] 李硕[1] 匡红[1] 敬新蓉[1] 闵敏[1] 陈健[1] 

机构地区：[1]解放军第452医院血液肿瘤中心,成都610021 [2]解放军第452医院核医学科,成都610021

出　　处：《肿瘤》2010年第5期395-400,共6页Tumor

基　　金：四川省卫生厅科学研究项目(编号:050287;050288)

摘　　要：目的:探讨负载自身肿瘤裂解物的树突状细胞(dendritic cells,DCs)联合细胞因子诱导杀伤(cytokine induced killer,CIK)细胞治疗肺腺癌的临床疗效及安全性。方法:选择30例肺腺癌患者,分离获得外周血单个核细胞(peripheral bloodmononuclear cells,PBMCs),其中贴壁细胞经重组人粒细胞巨噬细胞集落刺激因子(recombinant human granulocyte-macrophage colony stimulating factor,rhGM-CSF)和重组人白细胞介素-4(recombinant human interleukin-4,rhIL-4)诱导产生DCs,并负载自体肺腺癌细胞裂解物,培养获得Ag-DCs;悬浮细胞经干扰素-α(interferon,IFN-α)、白细胞介素-2(interleukin-2,IL-2)、抗CD3单克隆抗体和白细胞介素-1α(interleukin-1α,IL-1α)体外诱导产生CIK细胞;将Ag-DCs与CIK细胞共培养,观察CIK细胞体外对肺腺癌细胞株A549和自体肿瘤细胞的杀伤活性;30例患者接受Ag-DCs+CIK细胞过继免疫治疗,观察疗效。结果:Ag-DCs与CIK细胞共培养后,提高了CIK细胞对A549细胞和自体肿瘤细胞的杀伤活性;Ag-DCs联合CIK细胞治疗肺腺癌,可增强患者细胞免疫功能,改善生活质量,提高临床疗效;除一过性发热和畏寒外,未见其他不良反应。结论:Ag-DCs联合CIK细胞可作为中晚期肺腺癌的一种有效治疗手段。Objective：This study was to investigate the clinical efficacy and safety of autologous tumor cell lysate-pulsed dendri-tic cells（Ag-DCs） in combination with cytokine-induced killer（CIK） cells for lung adenocarcinomas.Methods：Peripheral blood mononuclear cells（PBMCs） were isolated from 30 patients with lung adenocarcinoma,and cultured with recombinant human granulocyte-macrophage colony stimulating factor（rhGM-CSF） and recombinant human interleukin 4（rhIL-4） to induce dendritic cells（DCs）.The DCs were pulsed with autologous tumor cell lysate.T lymphocytes from PBMC were incubated with interferon alpha（IFN-alpha）,IL-2,CD3 moAb,and IL-1α to induce CIK cells.The killing activity of CIK on lung adenocarcinoma A549 cells and autogenous tumor cells was investigated after CIK was co-cultured with Ag-DCs.The 30 patients received the immunotherapy with Ag-DCs and CIK.The immunologic and clinical responses were evaluated.Results：The killing activity of CIK cells on A549 and autologous tumor cells was increased remarkably after co-culture of CIK cells with Ag-DCs.Ag-DCs combined with CIK enhanced the immune function of lung adenocarcinoma patients,improved the living quality,and elevated the clinical efficacy.Except transient fever and chill,no remarkable adverse events were observed.Conclusion：Ag-DCs in combination with CIK cells was an effective adjuvant therapy for advanced lung adenocarcinomas.

关 键 词：肺肿瘤 腺癌 自身抗原 树突细胞 癌症疫苗 

分 类 号：R734.2[医药卫生—肿瘤]