【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;MTT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(P<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.更多还原

【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 granulocyte/macrophage-colony stimulating factor(GM-CSF) and interleukin-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.更多还原