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本研究目的是评价NOD/SCID小鼠皮下移植瘤模型对多发性骨髓瘤基因修饰瘤苗引发体内抗肿瘤反应的效果。首先给NOD/SCID小鼠腹腔注射人外周血淋巴细胞以在其体内重建人的免疫系统,然后皮下接种γ-射线灭活的基因修饰骨髓瘤细胞sko-007(表达绿色荧光蛋白或者p53、GM-CSF和B7-1基因),以PBS作为对照,最后植入活sko-007细胞进行攻击。结果发现,与对照组相比接种感染腺病毒Ad-p53/GM-CSF/B7-1的sko-007细胞可以明显抑制移植瘤生长,病理分析显示移植瘤纤维组织增生伴弥漫性坏死增多,血管增生显著。免疫组织化学染色显示瘤灶内有人T淋巴细胞浸润。结论: p53、GM-CSF和B7-1基因修饰的骨髓瘤细胞能够诱导产生抗肿瘤免疫反应,有可能用于人类多发性骨髓瘤的免疫治疗。
The purpose of this study was to evaluate the effect of NOD / SCID mouse subcutaneous xenograft model on the in vivo anti-tumor response of multiple myeloma gene-modified vaccine. NOD / SCID mice were first injected intraperitoneally with human peripheral blood lymphocytes to reconstitute the human immune system in vivo and then subcutaneously inoculated with gamma-ray inactivated genetically modified myeloma cells sko-007 (expressing green fluorescent protein or p53, GM -CSF and B7-1 gene), PBS as a control, and finally into live sko-007 cells for attack. The results showed that inoculation of sko-007 cells infected with adenovirus Ad-p53 / GM-CSF / B7-1 could significantly inhibit the growth of xenografts compared with the control group. The pathological analysis showed that the proliferation of fibrous tissue accompanied by diffuse necrosis and vascular Hyperplasia significantly. Immunohistochemical staining showed that there was human T lymphocyte infiltration in the tumor focus. Conclusion: The myeloma cells modified by p53, GM-CSF and B7-1 gene can induce anti-tumor immune response and may be used in the immunotherapy of human multiple myeloma.