糖基化修饰的DC疫苗特异性抗骨髓瘤活性的体外研究.pdfVIP

熊 红等 糖基化修饰的DC疫苗特异性抗骨髓瘤活性的体外研究 第7期 · 629· 糖基化修饰的DC疫苗特异性抗骨髓瘤活性的体外研究① 熊 红 吴秋业② 廖洪利② 赵庆杰② 侯 健 (第二军医大学长征医院血液科，上海200003) 中国图书分类号 R733．3 文献标识码 A 文章编号 1000-484X(2007)07-0629-05 [摘 要] 目的：探讨经过糖基化修饰改造过的肿瘤相关糖抗原冲击树突状细胞(DC)制备的DC疫苗特异性抗骨髓瘤 作用。方法：采用化学方法及肿瘤细胞的生物工程法使骨髓瘤细胞表达新肿瘤相关抗原N一丙酰多聚唾液酸(NPrPSA)；在无 血清培养条件下，采用GM—CSF／IFN一0【及TNF一0【从MM患者外周血单核细胞诱导培养DC。然后用表达新抗原的肿瘤细胞冲击 DC制备DC疫苗，将其刺激T细胞后，通过LDH释放法观察其对骨髓瘤细胞的杀伤效力，并采用ELISA法测定了T细胞分泌 细胞因子IFN一 的能力。结果：糖基化修饰的CD138 Npr—DC组LDH释放率较CD138 未修饰DC组明显增高(P0．01)。 CD138 Npr—DC组T细胞分泌IFN一 与CD138 未修饰DC组相比亦明显增加(P0．05)，而CD138一Npr—DC组与CD138一未 修饰DC组之间无统计学意义(P0．05)。结论：糖基化修饰的DC疫苗可以有效地激活Thl细胞免疫应答，分泌高水平的细 胞因子IFN一 ；可诱导出较普通DC疫苗更明显的抗骨髓瘤作用，并具有一定的安全性。 [关键词] 多发性骨髓瘤；树突状细胞；疫苗；肿瘤相关糖抗原 In vitro investigation on specific anti-myeloma activity of the glycOengineering modified dendritic cell vaccine XIONG舶ng， U Qiu—Ye，LIAO Hong—Li，ZHAO Qing—Jie，HOU Jian．Department ofHematology，Changzheng Hospital，Second Military Medical College，Shanghai 200003，China [Abstract] Objective：To explore the specific anti—myeloma effect of the dendritic cell vaccine pulsed with tumor associated carbohydrate antigen modified by glycoengineering．Methods：With chemical and biological engineering methods，the new antigen，N— propionyl polysialic acid(NprPSA)．Was expressed on myeloma cells．Monocytes were cultured witll seFLIm—free culture medium contai— ning GM—CSF／IFN一0【and TNF一0【to develop DC．which was pulsed with myeloma cells expressing the novel antigen to develop DC vac— cine．After the autologous T cells were stimulated with the vaccine．the capability for killing the myeloma cells was observed by LDH release．And the IFN一 secreted from T cells was detected by ELISA．Results：The LDH release in the modified CD138 Npr—DC group Was significantly higher than that in the CD138 unmodified DC group(P0．O1)．The secretion of IFN一 by the primed T cells Was enhanced remarkably in CD138 Npr—DC group in comparison with CD138 unm