CAJ | 학술논문

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.
본연구목적시평개NOD/SCID소서피하이식류모형대다발성골수류기인수식류묘인발체내항종류반응적효과.수선급NOD/SCID소서복강주사인외주혈림파세포이재기체내중건인적면역계통,연후피하접충γ-사선멸활적기인수식골수류세포sko-007(표체록색형광단백혹자p53、GM-CSF화B7-1기인),이PBS작위대조,최후식입활sko-007세포진행공격.결과발현,여대조조상비접충감염선병독Ad-p53/GM-CSF/B7-1적sko-007세포가이명현억제이식류생장,병리분석현시이식류섬유조직증생반미만성배사증다,혈관증생현저.면역조직화학염색현시류조내유인T림파세포침윤.결론:p53、GM-CSF화B7-1기인수식적골수류세포능구유도산생항종류면역반응,유가능용우인류다발성골수류적면역치료.
This study was aimed to evaluate the in vivo antitumor effect of genetically modified myeloma cell vaccine on human myeloma xenografts implanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID)mice. Human immune system was established in NOD/SCID mice by intraperitoneal injection of human peripheral blood lymphocytes (PBLs). After being inoculated subcutaneously with irradiated myeloma cell line sko-007, adenovirally transferred with GFP or p53, granulocyte-macrophage colony-stimulating factor (GM-CSF) and B7-1 genes, huPBLNOD/SCID mice were challenged by subcutaneous injection of non-transferred sko-007 cells. The results indicated that Ad-p53/GM-CSF/B7-1-infected sko-007 cell vaccination significantly reduced local tumor growth compared with controls. Histopathological and immunohistochemical analysis showed that tumor tissues increasingly displayed diffuse necrosis, mainly caused by apoptosis, accompanied with significant fibroplasias and blood vessel hyperplasia, and human T cells infiltrated into the tumor tissues. It is concluded that transgenic p53, GM-CSF and B7-1 expression produces an immune response against myeloma cells and may be of therapeutic value for multiple myeloma in human being.