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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(英文)

Biological characters of cytotoxic T lymphocytes transfected with tumor necrosis factor alpha gene and its antitumor effects on transplanted carcinoma in nude mice
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摘要 背景肿瘤患者体内的抗肿瘤免疫受到抑制。增强细胞毒性T淋巴细胞(cytotoxicTlymphocyte,CTL)的活性是提高过继免疫治疗效果,促进肿瘤康复的有效途径之一。目的对转导肿瘤坏死因子(TNF-α)基因的CTL的生物学特性及抗肿瘤活性进行研究,探讨细胞因子基因疗法和过继免疫治疗肿瘤的新途径。设计随机区组实验研究。地点和对象实验在广西医科大学医学实验中心完成。从人肝细胞癌组织中分离淋巴细胞,用BEL7404和IFN-г诱导得到CTL。BALB/c裸小鼠28只,雄性,4~6周龄,体质量18~20g,购自北京医科大学实验动物科学部(SPF级,合格证书医动字第01-3048号)干预用重组反转录病毒载体介导对CTL进行TNF-α基因转导。于每只裸鼠右前肢腋窝皮下注射注射BEL7404,建立荷瘤裸鼠模型,28只裸鼠按体质量分为4组,每组7只。观察转基因CTL对肿瘤原位(右前肢腋窝)及异位(左前肢腋窝皮下)注射治疗效果,分别用生理盐水注射治疗作对照。主要观察指标①检测TNF-α基因转导前后CTL的生长形态,增殖能力,TNF-α分泌量、细胞表型。②体外不同作用时间和效靶比浓度对BEL7404的杀伤效应。③各实验组的肿瘤生成时间,生长速度及肿瘤生成率。结果转基因CTL的生长形态、增殖活性及细胞表型与CTL相似,但具有持续、高效表达TNF-α的能力。 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 αgene 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.MAIN OUTCOME MEASURES:①The morphology, proliferation, and phenotype of CTL and the secretion of TNF αbefore or after TNF αgene transduction. ②Killing effects of different in vitro action time and density of effector/target cell ratio on BEL7404. ③Tumor generation period, growth 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]
出处 《中国临床康复》 CSCD 2004年第23期4934-4936,共3页 Chinese Journal of Clinical Rehabilitation
基金 广西教育厅重点科研资助项目(桂教19982-8)~~
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