恶性实体瘤患者自体细胞因子诱导杀伤细胞过继免疫治疗的安全性改进  

Improving safety of adoptive immunotherapy with auto-cytokine-induced killer cells in the patients with malignant solid tumor

作　　者：撒亚莲[1] 华映坤[1] 严新民[1] 贾玲[2] 张丽萍[1] 邹云莲[1] 宋建新[3] 

机构地区：[1]云南省第一人民医院,临床基础医学研究所,昆明650032 [2]云南省第一人民医院肿瘤科,昆明650032 [3]云南省第一人民医院临床检验中心,昆明650032

出　　处：《中国肿瘤临床与康复》2006年第6期494-497,共4页Chinese Journal of Clinical Oncology and Rehabilitation

摘　　要：目的观察恶性实体瘤患者外周血来源的细胞因子诱导杀伤细胞在自体血浆中的增殖特性及静脉回输治疗的安全性。方法用淋巴细胞分离液分离获取50例恶性实体瘤患者外周血单个核细胞,在含10%自体血浆的RPMI-1640培养液中添加rhIFN-γ、Anti-CD3mAb和rhIL-2联合诱导单个核细胞为细胞因子诱导杀伤细胞。在培养第13天进行细胞计数,通过流式细胞术检测细胞免疫表型,并将细胞进行自体回输。结果在培养第13天,细胞因子诱导杀伤细胞得到大量扩增,细胞数增加30.0±5.2倍。CD3+、CD3+CD4+、CD3+CD8+和CD3+CD16+CD56+细胞在培养第13天分别占(93.0±6.1)%、(28.4±7.2)%、(65.5±4.5)%和(25.8±12.2)%。恶性实体瘤患者回输自体细胞因子诱导杀伤细胞的治疗过程中未观察到明显的毒副作用,主要表现有畏寒、发热。结论恶性实体瘤患者血浆可以高效扩增自体细胞因子诱导杀伤细胞,临床应用安全可靠,且无明显的毒副作用。Objective To evaluate the ability of proliferation of cytokine-induced killer ceils cultured in autologous serum,which were derived from malignant solid tumor patients, and assess the safety of transfusion of them intravenously. Methods Peripheral blood mononuclear cells （PBMCs） from 50 patients with malignant solid tumor were separated by fractionation on Ficoll-Hypaque gradient, and cultured in the RPMI-1640 medium containing 10% autologous serum, then were induced into cytokine-induced killer ceils by recombinant human interferon-γ （rhIFN-γ）, recombinant human interleukin-2 （rhIL-2） and anti- CD3mAb. Cell densities were determined on d13 ,and the phenotypic patterns of cytokine-induced killer ceils were characterized by flow cytometry. The cultured cytokine-induced killer ceils were transfused back to the patients. Results The cytokine-induced killer cells got obvious proliferation after 13 days of culture, increased by （30.0±5.2） folds,and the percentages of CD3^± ,CD3^± CD4^±,CD3^± CD8^± and CD3^± CD16^± CD56 ^± cells were（93.0 ± 6.1 ） %, （28.4 ± 7.2） %, （65.5 ± 4.5 ） % and （ 25.8 ± 12.2 ） % respectively. Except temporal fever, chili and fatigue, no severe side effects were observed during or after cytokine-induced killer cells transfusion. Conclusion The results indicate that 10% autologous serum can culture cytokineinduced killer ceils which multiply effectively from the patients with malignant solid tumor. Transfusion of them is a safe and promising treatment,and has few side effects.

关 键 词：自体 杀伤细胞 细胞过继免疫治疗 安全性 实体瘤 

分 类 号：R730.5[医药卫生—肿瘤]