IL-2基因修饰的细胞毒T淋巴细胞抗肿瘤效应的研究  

Enhanced Antitumor Effect of Cytotoxic T Lymphocytes Modiated by IL-2 Gene

作　　者：吕彦恩[1] 曹雪涛[2] 于益芝[2] 弥静[2] 雷虹[2] 

机构地区：[1]北京军区总医院神经外科,北京100700 [2]第二军医大学免疫学教研室,上海200433

出　　处：《癌症》2001年第8期844-847,共4页Chinese Journal of Cancer

摘　　要：目的:了解IL2基因修饰的细胞毒T淋巴细胞(cytotoxicTlymphocytesCTL)的增殖和杀伤活性,探索细胞因子基因疗法及被动免疫治疗脑胶质瘤的新途径。方法:用昆明种小鼠的脾细胞体外诱导CTL,用腺病毒载体转染IL2基因,观察其体外增殖活性和杀伤活性,再用G422小鼠胶质母细胞瘤细胞建立肺转移瘤模型,36h后经过继回输,2周后计数肺的肿瘤结节,观察IL2基因转染的CTL对实验性肺转移瘤的治疗作用。结果:重组腺病毒载体在MOImultiplicityofinfection为100时,转染率达96.8%,IL2基因修饰的CTL增殖活性、IL2的分泌(248u)和体外杀伤活性36.4%明显增强,对实验性肺转移瘤的治疗作用都显著增强,肺转移结节数28显著减少(P<0.01)。结论:IL-2基因转染的CTL过继回输,可直接杀伤和诱导激活机体特异性抗肿瘤免疫反应,使体内抗肿瘤效果显著增强,有效抑制实验性肺转移瘤的生长,为胶质瘤的过继免疫治疗提供了新的思路和实验依据。Objective: To seek a new way of immunegene therapy for glioma through study on proliferation and cytotoxicity of interleukin 2(IL 2) gene transfected cytotoxic T lymphocytes(CTL). Methods: Transfected IL 2 gene with adenovirus vector on CTL induced from spleen cells of Kunming mice in vitro. Proliferation, secretion of interleukin 2,and cytotoxicity were determined.Thirty six hours after intravenous injection of viable G422 cells, mice were treated with intravenous injection of various CTL. Three days later, the treatment was repeated. The metastatic nodules in the lung were counted two weeks after the tumor challenge. Results: The transfected rate of adenovirus vector was 96.8% as multiplicity of infection(MOI) was 100. IL 2 gene transduction of CTL induced a increased proliferation(0.935), secretion of interleukin 2(248 u),and cytotoxicity(36.4%) in vitro and resulted in markedly reduced numbers of lung metastatic nodules(28)(P< 0.01). Conclusion:IL 2 gene introduced CTL exerts an increased antitumor response in the adoptive treatment models. Our findings provide experimental basis and a new idea of immune therapy for glioma. However, the experiment was study on the immunological mechanism of treatment for lung metastatic tumor with IL 2 gene transfected CTL, the antitumor effect of IL 2 gene transfected CTL in brain needs to be further studied.

关 键 词：白细胞介素2 基因转染 细胞毒T淋巴细胞 胶质瘤 

分 类 号：R730.3[医药卫生—肿瘤]