中国临床康复2004，Vol.8Issue(23)：4934-4936,3.
转基因细胞毒性T淋巴细胞的生物学特性及其对荷瘤裸鼠的抗肿瘤作用
Biological characters of cytotoxic T lymphocytes transfected with tumor necrosis factor-alpha gene and its antitumor effects on transplanted carcinoma in nude mice
摘要
Abstract
BACKGROUND: Antitumor immunity is suppressed in patients with tumor. It is an effective way to improve the efficacy of adoptive immunity therapy and promote rehabilitation by enhancing the cytokine activity of cytotoxic T lymphocyte (CTL).OBJECTIVE: To study the biological characters and antitumor effects of cytotoxic CTL transfected with tumor necrosis factor-α(TNF-α) gene, and seek a new way of immunegene therapy and adoptive immunity therapy for the treatment of tumor.DESIGN: Block randomizaed experiment.SETTING and MATERIALS: The experiment was done in the Center of Laboratory of Guangxi Medical University. CTL was obtained from lymphocytes isolated from human hepatocellular carcinoma tissue, and stimulated by BEL7404 cells and interferon γ(IFN-γ) . A total of 28 male BALB/c nude mice(aged 4 -6 weeks and weighing 18 -20 g) obtained from the Department of Experimental Animal Sciences of Peking University Health Sciences Center(SPF grade; certificate number: 01-3048).INTERVENTION: CTL was transfected with TNF-α gene by gene recombinant retrovirus vector. The models of tumor nude mice were established by injecting BEL7404 in the armpit of the right forelimb of these nude mice.Twenty-eight nude mice were divided into 4 groups according to their weights, with 7 mice in each group. The efficacy of transgene CTL on tumor in situ(armpit of right forelimb) and ex situ(armpit of left forelimb) were observed. Mice injected with normal saline were taken as the control group.phenotype of CTL and the secretion of TNF-α before or after TNF-α gene rate and tumor generation rate.RESULTS: The morphology, proliferation activity, and cell phenotype of the transgene CTL were similar to CTL. However, the transgene CTL could continuously and efficiently secret TNF-α, with an expression dose as high as 410 ng/L in 72 hours. The transgene CTL had a strong cytotoxic activity on BEL7404 in vitro; its cytotoxic acti] vity was positively correlated with the action period and the effector/target cell(E/T) ratio. The cytotoxic activity reached nearly 100% when the E/T ratio reached 20: 1. The cytotoxic activity of transgene CTL was significantly higher than that of CTL when the E/T ratio was 5:1 or 20:1 ( q = 7. 965 8, 4. 189 7, P ＜ 0. 05). Compared with control group, after the nude mice were treated with adoptive immunity therapy by transgene CTL, tumor generation speed, generation rate, and growth rate significantly decreased in transplanted carcinoma( P ＜ 0.05).CONCLUSION: TNF-α gene introduced CTL can continuously express TNF-α, and has a good antitumor activity. The construction of transgene CTL canprovide a new effector cell for adoptive immunity therapy, and may play an important role in controlling the metastasis and recurrence of tumors.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/免疫疗法,过继分类
医药卫生引用本文复制引用
罗意革,陆云飞,邱庆明..转基因细胞毒性T淋巴细胞的生物学特性及其对荷瘤裸鼠的抗肿瘤作用[J].中国临床康复,2004,8(23):4934-4936,3.基金项目
广西教育厅重点科研资助项目(桂教19982-8) （桂教19982-8）
