阻抑同种异体骨髓移植受者肿瘤逃逸的实验研究

In this study, the expression of Fas ligand on leukemia cells was detected. It showed that leukemia cells express more membrane Fas ligand (30.64±5.71)% than normal ones （0.36±0.16）%（P＜0.01）. And the expressed Fas ligand could partly induce the apoptosis of Fas+ Jurkat cells. The soluble Fas gene of murine and human being were successfully cloned. And their eukaryotic expression vectors were successfully constructed and could express soluble Fas protein in vitro. Apoptosis inducing test showed that the expression of the soluble Fas could block the Fas-induced apoptosis, which proved the biological activity of the recombinant soluble Fas. The recombinant adenoviral vectors with soluble Fas gene were successfully generated with the method of homologous recombination between two plasmids in Escherichia coli. The mice models of leukemia/ lymphoma constructed by inoculating C57BL/6 mice (H-2b) with EL4 cell through caudal vein were acted as the receptor for bone marrow transplantation. Donors of BM grafts were autologous male mice. The bone marrow mononuclear cells of the donors, transducted with soluble Fas gene by infecting with adenovirus vector were transplanted to the receptors which were sublethal irradiated before. It showed that, contrasted with the control group, the survival and complete remission rates of the subjects group were significantly increased (P＜0.01). It showed that the transfer of soluble Fas gene by adenovirus could block the effect of the immune escape of EL4 cells through Fas ligand in receptor mice. after bone marrow transplantation.

构建可溶性Fas基因，将其转入供者早期造血祖细胞，并移植给受者。骨髓造血功能重建后沙中泶锟扇苄訤as，封闭肿瘤细胞所表达的FasL。阻断肿瘤细胞通过Fas/FasL途径介导的肿瘤特异性淋巴细胞凋亡，探讨终止“肿瘤免疫逃逸”的有效对策，以提高骨髓移植疗效，为今后借助基因治疗减少骨髓移植后恶性肿瘤的复发提供实验和理论依据。