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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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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 。 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.
出处 《肿瘤防治杂志》 2003年第8期795-798,共4页 China Journal of Cancer Prevention and Treatment
基金 广西教育厅重点科研资助项目 (桂教 19982 -8)
关键词 T淋巴细胞 细胞毒性 肿瘤坏死因子 肝肿瘤/病理学 基因疗法 免疫治疗 过继 lymphocyte,cytotoxic tumor necrosis factor liver neoplasms/pathology gene therapy immunity therapy,adoptive
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