腺病毒介导CD269基因修饰树突状细胞体外治疗多发性骨髓瘤  

Treatment of multiple myeloma of adenovirus-mediated CD269 gene-modified dendritic cells in vitro

作　　者：李清照 胡国瑜 沈婵娟 谭奎 刘玉霞 袁朝晖 

机构地区：[1]株洲市中心医院,湖南株洲412000

出　　处：《现代医学》2017年第10期1400-1404,共5页Modern Medical Journal

基　　金：湖南省卫计委资助项目(C2015-75)

摘　　要：目的:探讨腺病毒介导CD269基因修饰树突状细胞(DC)的生物学特性及体外治疗多发性骨髓瘤(MM)的效果。方法:通过基因重组技术改建一种携B细胞成熟抗原(BCMA)CD269基因的无毒性腺相关病毒,感染DC后刺激产生杀伤MM细胞的特异性细胞毒性T淋巴细胞(CTLs)。采用流式细胞仪分析CTLs的γ干扰素(IFN-γ)表达情况,采用MTS实验检测CTLs对MM原代细胞的杀伤率及效靶比。结果:CTLs IFN-γ的表达率为29.07%,明显高于对照组的13.95%(P<0.05)。MTS实验表明,培养出来的CTLs对MM细胞株U266的杀伤率达到(32.53±2.92)%,对MM病人原代细胞的杀伤率为(28.23±3.11)%,而对正常病人原代细胞的杀伤率仅为(22.11±2.54)%。随着效靶比的升高,杀伤率增高。结论:实验所构建的CD269抗原病毒能刺激培养出针对MM的特异性杀伤细胞,为临床细胞治疗奠定了有效的实验基础。Objective： To investigate the biological characteristics of adenovirus- mediated CD269 gene- modified dendritic cells and the effect of treatment of multiple myeloma （MM） in vitro. Methods： A non-toxic gonadal associated virus carrying B cell maturation antigen gene was constructed by gene recombination technique, and the infected dendritic cells were stimulated to produce specific cytotoxic T lymphocytes （ CTLs ） killing MM. The expression of IFN-＇y in CTLs was analyzed by flow cytometry. The killing rate and effective target ratio of CTLs to primary myeloma cells were detected by MTS. Results ： The expression rate of IFN-γ in CTLs was 29.07%, which was significantly higher than that in the control group （ 13.95%, P 〈 0.05 ）. MTS experiments showed that the killing rate of the cultured CTLs for the multiple myeloma cell line U266 was （32.53± 2.92 ） %. And the killing rate of the primary cells of the patients with multiple myeloma was （28.23 ±3. 11 ） %. The killing rate of the cultured CTLs for normal primary cells was only （22. 11 ±2.54） %. With the increasing of the effect- to- target ratio, the killing rate increased. Conclusion： The CD269 antigen constructed by the experiment can stimulate the specific killing cells against the myeloma and provide an effective experimental basis for the clinical therapy.

关 键 词：腺相关病毒 CD269基因 细胞毒性T淋巴细胞 多发性骨髓瘤 

分 类 号：R733.3[医药卫生—肿瘤]