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转基因CTL的构建及其生物学特性的研究

Construction of Cytotoxic T Lymphocyte (CTL) Transduced with TNF-α Gene and the Study of Its Biological Characters

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【作者】 罗意革陆云飞邱庆明

【Author】 LUO Yi-ge,LU Yun-fei,QIU Qing-ming.Department of Pediatric Surgery,the First Affiliated Hospital,Guangxi Medical University,Nanning 530021,China

【机构】 广西医科大学第一附属医院小儿外科广西医科大学第一附属医院胃肠腺体外科广西医科大学第一附属医院医学实验中心 广西南宁530021广西南宁530021广西南宁530021

【摘要】 目的 :构建TNF α基因转染的CTL ,并对其生物学特性进行研究。方法 :用重组逆转录病毒载体介导将TNF α基因导入CTL ,构建转基因CTL。检测其增殖能力 ,TNF α分泌量、细胞表型 ,观察其对BEL74 0 4的体内、外抗肿瘤活性。结果 :转基因CTL的形态、增殖活性及细胞表型与CTL相似。但具有高效表达TNF α的能力 ,72h表达量为 4 10pg mL。转基因CTL对BEL74 0 4具有较高的体外杀伤作用 ,其杀伤活性与作用时间及效靶细胞比正向相关。转基因CTL对荷瘤裸鼠过继免疫后 ,移植瘤的生成延迟、生长减慢 ,成瘤率降低。结论 :转基因CTL的构建为肿瘤过继免疫治疗提供新型的效应细胞 ,具有进一步研究的价值

【Abstract】 Objective To study the biological characters of cytotoxic lymphocyte (CTL) transduced with TNF-α gene.Methods Gene-transduced CTL was constructed by using the recombinant retroviral vector to transfer TNF-αgene into CTL.The secretion of TNF-α,and the cell phenotype and proliferation activity were detected.The cytotoxic activity of gene-transduced CTL was investigated in vitro and in vivo.Results The shape and proliferation activity and the cell phenotype of gene-transduced CTL were similar to CTL.Furthermore,gene-transduced CTL could secret TNF-α continuously,its expression dose was 410 pg/mL in 72 h.Gene-transduced CTL had strong cytotoxic activity on BEL7404 in vitro,their cytotoxic activity were positive correlated with the effecting period and the ratio of effector-target cell.After treated with adoptive immunity therapy by gene-transduced CTL,a stronger inhibition effect to tumor generation speed,generation rate,and growth speed was exhibited in transplanted carcinoma in nude mice.Conclusions The construction of gene-transduced CTL provides a new effector cell for the adoptive immunity therapy against tumor.Gene-transduced CTL has the value of further study.

【基金】 广西教育厅重点科研资助项目 (桂教 19982 -8)
  • 【文献出处】 肿瘤防治杂志 ,Journal of Qilu Oncology , 编辑部邮箱 ,2003年08期
  • 【分类号】R73-3
  • 【下载频次】33
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