转移性去势抵抗性前列腺癌八例自然杀伤细胞治疗  

Eight cases of metastatic castration resistant prostate cancer treated with autologous natural killer cells

作　　者：高鹏[1] 单玉喜[1] 薛波新[1] 

机构地区：[1]苏州大学附属第二医院泌尿外科,215004

出　　处：《中华实验外科杂志》2017年第12期2038-2041,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨转移性去势抵抗性前列腺癌（mCRPC）患者自体外周血自然杀伤（NK）细胞输注的治疗效果及安全性。方法连续选择2014年1月至2015年6月的8例mCRPC患者，签署书面的知情同意并完成相关实验室检查和评估。抽取50 ml外周血，利用Ficoll密度梯度离心获得外周血单核细胞，体外扩增后进行细胞纯度和杀伤能力检测。患者每周接受1次自体NK细胞回输，最后一次回输后第3天进行临床检测。比较治疗前后的NK细胞扩增情况、对肿瘤细胞杀伤情况、外周血细胞因子等指标变化以评价有效性和安全性。结果经过（18±3） d细胞因子诱导的体外扩增，NK细胞平均可达4.39×109个，CD3－CD56＋ NK细胞纯度平均达84.3%。NK细胞对K562及PC-3具有明显的杀伤作用，在效靶比10∶1时，对K562和PC-3的杀伤作用分别为82%和78%。7/8例患者外周血出现CD3－CD56＋ NK细胞的比例升高；6/8例患者外周血出现CD8＋ T细胞的比例升高（P＝0.078）；细胞因子白细胞介素（IL）-2、IL-12、干扰素（IFN）及肿瘤坏死因子（TNF）未见明显变化（P＝0.235）；生活质量改善（P＝0.012）；骨痛有一定缓解（P＝0.013）；未观察到相关的不良反应与不良反应。结论自体NK细胞回输可能一定程度唤醒mCRPC患者的免疫应答。ObjectiveTo evaluate the efficacy and safety of autologous natural killer （NK） transfusion to treat the patients of metastatic castration resistant prostate cancer （mCRPC）.MethodsEight consecutive patients of mCRPC were enrolled from Jan 2014 to Jun 2015 and written informed consent was provided. The patients were evaluated by using laboratory tests, medical imaging and scores. Fifty milliliter blood sample was drawn and the peripheral blood mononuclear cells （PBMCs） were isolated by Ficoll density centrifugation, then the NK population were induced to proliferate for approximately 1 000 times. The Patients received autologous NK transfusion every one week when the NK cells passed quality and functional tests. The patients were evaluated again three days following last transfusions （3-4 time in total）.ResultsThe averaged NK cells’ population were proliferated to 4.39×109 cells （range 3.36-6.44×109 cells） in （18±3） days. The purity of NK was 84.3% （range 68.8%-94.7%）. No pathogens, endotoxin and mycoplasma were detected. The NK cells could lyze the K562 and PC-3 cells at cell concentration ratio of 10∶1 and above for 4 hours, 82% and78% and above, respectively. The NK population were increased in 7/8 patients; and the CD8＋ T cells population were increased in 6/8 patients （P=0.078）; cytokine interleukin （IL）-2, IL-12, interferon （IFN） and tumor necrosis factor （TNF） did not show significant variation （P=0.235）. The quality of life （Kamofshy score） and ostealgia （numeric rating scale, NRS） were ameliorated. No adverse events were observed.ConclusionTo some extent, the immune response of mCRPC patients could be evoked following autologous NK cells transfusion.

关 键 词：自然杀伤(NK)细胞 细胞治疗 前列腺癌 抵抗性 转移性 去势 细胞因子白细胞介素 自体外周血 

分 类 号：R737.25[医药卫生—肿瘤]