多发性骨髓瘤基因修饰瘤苗诱导体内抗肿瘤反应的实验研究(英文)  

Genetically Modified Myeloma Cell Vaccine Inducing Antitumor Immune Response in vivo

作　　者：任素萍[1] 王立生[1] 郭强[1] 王华[1] 贾向旭[1] 徐娟[2] 王恒湘[3] 吴祖泽[1] 

机构地区：[1]北京放射与辐射医学研究所实验血液学研究室,北京100850 [2]北京宣武医院血液科,北京100053 [3]空军总医院血液科,北京100036

出　　处：《中国实验血液学杂志》2006年第1期54-60,共7页Journal of Experimental Hematology

基　　金：This project was supported in part by Chinese National Basic Researchand Development Grants '973 ' ( No. 2004CB518801 and No. 2002CB713804);Chinese High-Tech Program '863' (No. 2003AA216050);Chinese National Science Foundation (No.30400189).

摘　　要：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。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, huPBL- NOD/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.

关 键 词：多发性骨髓瘤 骨髓瘤细胞疫苗 抗肿瘤免疫反应 免疫治疗 

分 类 号：R733.3[医药卫生—肿瘤] R730.51[医药卫生—临床医学]