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[骨髓瘤独特型蛋白脉冲树突状细胞疫苗诱导的体外抗骨髓瘤效应]

[In vitro anti-myeloma effects induced by myeloma idiotype-protein pulsed dendritic cell vaccine].

作者信息

Zhang Mei, Yin Xiao-Ran, Luo Yun-Ya, Lin Xiu, Wang Meng-Chang, He Peng-Cheng, Li Jing, Guo Gui-Li, Cai Rui-Ho, Liu Ya-lin

机构信息

Department of Hematology, First Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2005 Oct;26(10):593-7.

PMID:16532967
Abstract

OBJECTIVE

To investigate the specific antitumor immune response induced by idiotype protein (Id)-pulsed dendritic cells (DC) in vitro.

METHODS

DC was generated from peripheral blood monocytes of the multiple myeloma (MM) patients using GM-CSF, IL-4, and TNF-alpha. The DCs were pulsed with idiotypic fragment, the F(ab')2 fragment of M protein from MM patient at the immature stage. The morphologic characteristics of the cells were observed with light and electron microscopes. The phenotypic features were analyzed with FACS, MTT assay was employed to evaluate the proliferation of autologous T cells and the inhibition rate of MM cells.

RESULTS

DC precursors in peripheral blood could be induced to typical mature DC in medium containing GM-CSF, IL-4 and TNF-alpha. Mature DC with Id could increase the proliferation of the autologous T cells and activate naive T cells to become tumor specialized cytotoxic T lymphocytes (CTL). The CTL at different doses showed significant inhibition on or killing ability to autologous MM cells in vitro.

CONCLUSIONS

In a suitable cytokine environment, the DC precursors from peripheral blood of MM patients could be induced to functional DC, and vaccination of Id-pulsed DC could induce active antitumor immune response.

摘要

目的

研究独特型蛋白(Id)脉冲树突状细胞(DC)在体外诱导的特异性抗肿瘤免疫反应。

方法

使用GM-CSF、IL-4和TNF-α从多发性骨髓瘤(MM)患者的外周血单核细胞中生成DC。在未成熟阶段,用独特型片段(MM患者M蛋白的F(ab')2片段)脉冲DC。用光镜和电镜观察细胞的形态特征。用流式细胞术分析表型特征,采用MTT法评估自体T细胞的增殖及MM细胞的抑制率。

结果

在含有GM-CSF、IL-4和TNF-α的培养基中,外周血中的DC前体可被诱导为典型的成熟DC。携带Id的成熟DC可增加自体T细胞的增殖,并激活初始T细胞成为肿瘤特异性细胞毒性T淋巴细胞(CTL)。不同剂量的CTL在体外对自体MM细胞显示出显著的抑制或杀伤能力。

结论

在合适的细胞因子环境中,MM患者外周血中的DC前体可被诱导为功能性DC,接种Id脉冲DC可诱导主动抗肿瘤免疫反应。

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