肿瘤坏死因子α基因转导的肿瘤浸润淋巴细胞体外生物学活性及不同转输方式的比较(英文)  

Bioactivity of in vitro cultured tumor necrosis factor-alfa transduced tumor-infiltrating lymphocytes and therapeutic effects on human brain glioblastoma infused in different ways

作　　者：关俊宏[1] 于宏伟[1] 潘尉然[1] 杨涌杰[1] 王成林[1] 任长山[2] 陈红[2] 隋承光[2] 

机构地区：[1]中国医科大学附属第二医院神经外科,辽宁省沈阳市110004 [2]中国医科大学肿瘤研究所,辽宁省沈阳市110001

出　　处：《中国临床康复》2005年第26期262-265,共4页Chinese Journal of Clinical Rehabilitation

基　　金：辽宁省自然科学基金项目资助(972250)~~

摘　　要：背景:利用肿瘤过继免疫和基因转移技术将表达肿瘤坏死因子α的载体导入运载细胞回输到体内,使肿瘤坏死因子α在肿瘤局部高浓度表达,既可增加肿瘤坏死因子α直接杀伤肿瘤细胞的能力,又能减少对其他组织的毒副作用。目的:探讨肿瘤坏死因子α基因转导的肿瘤浸润淋巴细胞体外生物学活性及不同转输方式对荷瘤裸鼠肿瘤细胞的抑制作用。设计:以实验动物为观察对象的随机对照实验。单位:中国医科大学肿瘤研究所。材料:实验于2000-01/2001-12在中国医科大学肿瘤研究所和中国医科大学实验动物部完成。TJ8510细胞(人脑恶性胶质瘤细胞系细胞):天津医科大学总医院神经病学研究所提供;实验动物:先天性无胸腺BALB/C裸鼠36只。方法:在肿瘤坏死因子α反转录病毒转移系统的建立及运载细胞肿瘤浸润淋巴细胞制备的基础上,利用构建的单克隆病毒细胞株PLC-2和PLJC-5将标记基因NeoR和目的基因肿瘤坏死因子α分别导入到肿瘤浸润淋巴细胞中,然后对其进行细胞增殖、肿瘤坏死因子表达、体外抗瘤活性的检测。将36只裸鼠接种肿瘤后随机分为6组,局部转输对照组、局部转输肿瘤浸润淋巴细胞组、局部转输肿瘤坏死因子肿瘤浸润淋巴细胞组、静脉转输对照组、静脉转输肿瘤浸润淋巴细胞组、静脉转输肿瘤坏死因子肿瘤浸润淋巴细胞组,对荷瘤裸鼠的治疗作用进行观察。主要观察指标:①基因转导前后肿瘤浸润淋巴细胞的增殖情况和肿瘤浸润淋巴细胞的肿瘤坏死因子α的表达。②体外抗瘤活性的测定。③动物实验结果。结果:①肿瘤浸润淋巴细胞、NeoR-肿瘤浸润淋巴细胞及肿瘤坏死因子肿瘤浸润淋巴细胞3组细胞的体外增殖活性差异无显著性意义(P>0.05)。②肿瘤浸润淋巴细胞与NeoR-肿瘤浸润淋巴细胞的肿瘤坏死因子α分泌量差异无显著性意义(P>0.05);而肿瘤坏死因子�BACKGROUND： Tumor-adopted immunity and gene transduction tech- nique are used to introduce tumor necrosis factor-α vector into carrier cells, which are then re-infused into the body so that cancer cells can be killed by tumor necrosis factor-α more directly and effectively with fewer side effects on the other tissues due to high local expression. OBJECTIVE： To study the bioactivity of in vitro cultured tumor necrosis factor-α transduced tumor-infiltrating lymphocytes as well as the inhibitory effects on cancer cells of cancer-loaded rats infused in different ways. DESIGN： A randomized controlled study based on experimental animals. SEETING： Cancer Research Institute of China Medical University. MATERIALS： This study was carried out at the Cancer Research Institute and the Experimental Animal Department, China Medical University, between January 2000 and December 2001. TJ8510 cell line （human brain glioblastoma cell line） was provided by the Neurological Research Institute of Tianjin Medical University Affiliated Hospital. The experimental animals were 36 BALB/C nude mice congenitally having no thymus. METHODS： Based on the establishment of tumor necrosis factor-α retroviral transduction system and the preparation of carrier cells tumor-infiltrating lymphocytes, the monoclonal virus cell line PLC-2 and PLIC-5 available were used to introduce marked gene NetR and targeted gene tumor necrosis factor-α into tumor-infiltrating lymphocytes, respectively. Then cell proliferation, tumor necrosis factor expression and in vitro antitumor activity were examined. After cancer cell inoculation, the 36 nude mice were randomly divided into 6 groups： local infusion control group, local tumor-infiltrating lymphocytes infusion group, local tumor necrosis factor-tumor-infiltrating lymphocytes infusion group, venous infusion control group, venous tumor-infiltrating lymphoeytes infusion group and venous tumor necrosis factor-tumor-infiltrating lymphoeytes infusion group, and the therapeutic effects on the cance

关 键 词：肿瘤坏死因子 基因疗法 神经胶质瘤 肿瘤浸润淋巴细胞 肿瘤坏死因子Α 体外生物学活性 基因转导 杀伤肿瘤细胞 随机对照实验 中国医科大学 

分 类 号：R730.5[医药卫生—肿瘤] R587.1[医药卫生—临床医学]