树突状细胞联合CIK细胞应用于晚期恶性实体瘤治疗的临床疗效观察

Clinical observation on the effect of co-treatment with autologous CIK cells and dendritic cells on advanced solid carcinoma

目的:研究树突状细胞(dendritic cells,DCs)和细胞因子诱导的杀伤细胞(cytokine induced killer,CIK)联合治疗晚期实体瘤的临床疗效。方法:选择110例晚期实体瘤患者,分离外周血单个核细胞(peripheral blood mononuclear cells,PBMCs),其中贴壁细胞用粒细胞巨噬细胞集落刺激因子(granulocyte-macrophage colony-stimulating factor,GM-CSF)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及白细胞介素-4(interleukin-4,IL-4)等诱导产生DCs,并用自体肿瘤细胞或外源性肿瘤细胞抗原致敏,获得Ag-DCs;悬浮细胞经干扰素-γ(interferon-γ,IFN-γ)、IL-2和CD3单克隆抗体(CD3monoclonal antibody,CD3mAb)等诱导产生CIK细胞,将DCs与CIK细胞共同培养;采用FCM法检测DCs及CIK细胞表型,并回输患者进行治疗。结果:42例可评价病灶的患者中,2例完全缓解(complete response,CR),9例部分缓解(partial response,PR),15例疾病稳定(stable disease,SD);37例不可评价病灶的患者中,25例患者有效,与治疗前相比,治疗后免疫功能及肿瘤标志物有一定程度改善。结论:DCs-CIK细胞联合治疗晚期恶性实体瘤安全有效,具有一定的临床应用前景。

Objective：To evaluate the therapeutic effect of cytokine induced killer （CIK） cells in combination with dendritic cells （DCs） on advanced solid tumor. Methods：Peripheral blood mononuclear cells （PBMCs） were isolated from 110 patients with advanced solid tumor. The adherent cells were cultured with granulocyte-macrophage colony-stimulating factor （ GM-CSF）, tumor necrosis factor （TNF）-alpha, and interleukin-4 （IL4） to induce DCs. The DCs were sensitized with antigens of autologous tumor cells or ex- trinsic tumor cell lines to produce Ag-DCs. Suspending ceils were cultured with interferonq, （IFN-γ）, interleukin-2 （IL-2）, and CD3 monoclonal antibody （CD3 mAb） to prepare CIK cells. Then, the CIK cells were co-cultured with DCs. The phenotype of DCs and CIK cells were analysed using flow cytometry. The autologous CIK cells and DCs were transfused into the patients who had advanced solid tumor. Results：In the 42 patients who were eligible for evaluation, 2 achieved complete remission （CR） ,9 partial remission （PR） and 15 stable disease （SD）. In the 37 patients who were not eligible for evaluation, 25 had efficient response. The immune function was improved and the level of tumor markers were altered significantly compared with those before treatment. Conclusion ： CIK cells in combination with DCs treatment is safe and effective in the treatment of advanced malignant solid tumors and has a better application foreground in clinic.