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-现代医学

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

单位：株洲市中心医院, 湖南株洲 412000

分类号：R733.3

出版年·卷·期（页码）：2017·36·第十期（1400-1404）

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-γ 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.

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