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微型双功能抗体在裸鼠体内介导人T细胞杀伤白血病细胞
引用本文:范冬梅,杨铭,赵英新,许元富,熊冬生,陈礼平,王敏. 微型双功能抗体在裸鼠体内介导人T细胞杀伤白血病细胞[J]. 中国免疫学杂志, 2011, 27(4): 312-315. DOI: 10.3969/j.issn.1000-484X.2011.04.006
作者姓名:范冬梅  杨铭  赵英新  许元富  熊冬生  陈礼平  王敏
作者单位:中国医学科学院、北京协和医学院血液学研究所、血液病医院、实验血液学国家重点实验室,天津,300020
基金项目:国家自然基金项目资助,天津市科技发展计划项目
摘    要:目的:研究抗CD3/抗CD19微型双功能抗体介导人T细胞对白血病细胞的特异性靶向杀伤活性。方法:利用Ficoll-Hypaque法分离外周血淋巴细胞(PBL),流式细胞术从中分选T淋巴细胞,FACS检测T细胞表面标记CD25和CD69激活后的表达变化,实时定量PCR检测各组穿孔素(Perforin)和颗粒酶A(Granzyme A)的释放,建立BALB/c裸鼠Raji细胞移植瘤模型,测定该双功能抗体介导的体内靶向杀伤活性。结果:激活的T细胞,双功能抗体组CD25和CD69的表达以及释放Perforin和Granzyme A的量均明显高于对照组,在对人白血病裸鼠移植瘤模型的生物治疗中,抗CD3/抗CD19微型双功能抗体能有效抑制白血病移植瘤的生长。结论:抗CD3/抗CD19微型双功能抗体在体外及动物肿瘤模型实验中能介导人T细胞有效杀伤白血病细胞,具有潜在的临床应用前景。

关 键 词:双功能抗体  CD19  CD3  非霍奇金淋巴瘤  免疫治疗

Specific targeted cytotoxicity to resistant leukemia cells mediated by anti-CD3/anti-CD19 diabody
FAN Dong-Mei,YANG Ming,ZHAO Ying-Xin,XU Yuan-Fu,XIONG Dong-Sheng,CHEN Li-Ping,WANG Min. Specific targeted cytotoxicity to resistant leukemia cells mediated by anti-CD3/anti-CD19 diabody[J]. Chinese Journal of Immunology, 2011, 27(4): 312-315. DOI: 10.3969/j.issn.1000-484X.2011.04.006
Authors:FAN Dong-Mei  YANG Ming  ZHAO Ying-Xin  XU Yuan-Fu  XIONG Dong-Sheng  CHEN Li-Ping  WANG Min
Affiliation:FAN Dong-Mei,YANG Ming,ZHAO Ying-Xin,XU Yuan-Fu,XIONG Dong-Sheng,CHEN Li-Ping,WANG Min.The State Key Laboratory of Experimental Hematology,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300020,China
Abstract:Objective:To study the specific targeted cytotoxicity to resistant leukemia cells medidated by anti-CD3/anti-CD19 diabody.Methods:Human peripheral blood lymphocytes(PBL) were isolated using Ficoll-Hypaque density-gradient centrifugation from heparinized blood of healthy volunteers and monocytes were depleted by adherence to plastic flasks.Also releasing of perforin and granzyme A,expressing the membrane molecular CD25 and CD69 on activated T cells of the same group,and apotosis of these T cells were analyze...
Keywords:CD19  CD3
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