多表位BCR-ABL融合抗原诱导特异性CTL抗慢性髓性白血病细胞的体外实验研究
In vitro specific anti-chronic myeloid leukemia cell effect of CTL induced by a multiple epitope BCR-ABL fusion protein
杜庆锋 1郑维扬 2周淑芸2
作者信息
- 1. 南方医科大学南方医院临床医学教育中心,广东广州510515
- 2. 南方医科大学南方医院血液科,广东广州,510515
- 折叠
摘要
目的:在应用基因工程技术人工表达获得多表位BCR.ABL融合蛋白的基础上,对该融合抗原在体外诱导对白血病细胞的特异性杀伤效应进行检测,探索慢性髓系白血病(CML)免疫治疗的新途径.方法:从外周血单个核细胞培养树突细胞(DC),以BCR-ABL融合抗原脉冲刺激DC,诱导特异性细胞毒淋巴细胞(CTL)产生;MTY法检测CTL对白血病靶细胞的特异性杀伤活性.结果:以BCR-ABL融合蛋白抗原刺激产生的CTL能特异性抑制b3a2+的靶细胞生长,包括K562细胞(P<0.01)和HLA-A2+/b3a2+的CML原代细胞(JP<0.05),而对HLA-A2-或b2a2+靶细胞无明显抑制作用.结论:我们所设计表达的多表位BCR-ABL融合抗原能在体外诱导特异性抗CML免疫反应,抑制b3a2+白血病细胞生长,有望为进一步的体内实验奠定基础.
Abstract
AIM: To assay the anti-leukemia effect of cytotoxic lymphocytes(CTLs) induced by a multiple epitope BCR-ABL fusion protein in vitro acquired by gene engineering technology so as to explore a new method of immunotherapy for chronic myeloid leukemia. METHODS: Dendritic cells ( DCs) were generated from peripheral mononuclear cells by co-cultivation with granulo-cyte/macrophage-colony stimulating factor ( GM-CSF) and inter-leukin-4(IL-4). Pulsed with the BCR-ABL fusion protein antigen, the harvested DCs were transformed into specific CTLs. The specific lytic activities of CTLs on target cells were detected by standard MTT assay. RESULTS: CTLs stimulated with the fusion protein inhibited the growth of b3a2 + target cells(P <0.05) , including K562 cells( P <0.01) and HLA-A2 +/b3a2 + CML cells ( P < 0. 05), but exerted no effect on HLA-A2-or b2a2 + target cells. CONCLUSION: The multiple epitope BCR-ABL fusion antigen in this study can induce specific anti-CML immunological reaction and inhibit the growth of b3a2 + leukemia cells in vitro, which may provide a research basis for further investigation on the strategy of immunotherapy for CML in vivo.
关键词
白血病,髓样,慢性/BCR-ABL/免疫疗法Key words
leukemia/myeloid/chronic/BCR-ABL/immunotherapy引用本文复制引用
基金项目
广州市科技攻关重点引导项目(06A121207)
出版年
2009
NETL
NSTL
维普
万方数据