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| 开发抗CD44抗体治疗急性髓系白血病 | |
| 引用本文： | 屈浩,张涛,张丽艳,张毅,王玫,王冬梅,何大水,黄丽华,朱卫彬,张宇光.开发抗CD44抗体治疗急性髓系白血病[J].生物化学与生物物理进展,2009,36(2):190-197. |
| 作者姓名： | 屈浩 张涛 张丽艳 张毅 王玫 王冬梅 何大水 黄丽华 朱卫彬 张宇光 |
| 作者单位： | 1. 北京协和医学院中国医学科学院血液学研究所血液病医院,天津,300020 2. 协和十细胞基工程有限公司,天津,300384 3. 北京协和医学院中国医学科学院血液学研究所血液病医院,天津300020;协和十细胞基工程有限公司,天津,300384 |
| 基金项目： | 天津市科技创新专项资金，天津市二十项自主创新产业化重大项目(08FDZDSH03000)资助项目. |
| 摘 要： | 为了探讨抗CD44 抗体对急性髓系白血病(AML)细胞增殖和分化的影响，为肿瘤靶向药物的开发提供前提和基础．应用流式细胞术检测抗CD44单克隆抗体HI313的亲和力，MTS检测HI313是否抑制NB4细胞生长，并检测细胞周期的变化，与初筛AML病人标本共培养检测其促分化作用．结果显示HI313抑制NB4细胞生长，能使细胞周期停留在 G0/G1期，并能有效诱导AML病人血细胞的分化．通过以上实验证明抗CD44抗体HI313对NB4细胞具有增殖抑制作用，作用机制可能与阻滞细胞周期于G0/G1期相关， 并对AML病人的细胞有一定的促分化作用，提示此抗体具有针对AML进行靶向治疗的潜力，为HI313人抗体的进一步基因工程改造及临床应用奠定了基础． |
| 关 键 词： | CD44抗体 细胞周期 促分化 抗体治疗 |
| 收稿时间： | 2008/5/16 0:00:00 |
| 修稿时间： | 2008/7/14 0:00:00 |
Development of Anti-CD44 Therapeutic Antibody for Acute Myeloid Leukemia |
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| QU Hao,ZHANG Tao,ZHANG Li-Yan,ZHANG Yi,WANG Mei,WANG Dong-Mei,HE Da-Shui,HUANG Li-Hu,ZHU Wei-Bin and ZHANG Yu-Guang.Development of Anti-CD44 Therapeutic Antibody for Acute Myeloid Leukemia[J].Progress In Biochemistry and Biophysics,2009,36(2):190-197. | |
| Authors: | QU Hao ZHANG Tao ZHANG Li-Yan ZHANG Yi WANG Mei WANG Dong-Mei HE Da-Shui HUANG Li-Hu ZHU Wei-Bin and ZHANG Yu-Guang |
| Institution: | Institute of Hematology & Hospital of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Institute of Hematology & Hospital of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China;Institute of Hematology & Hospital of Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;Union Stem Cell & Gene Engineering Company Limited, Tianjin 300384, China |
| Abstract: | An anti-CD44 monoclonal antibody, HI313, as a potential tool to treat Acute Myeloid Leukemia (AML) have been developed. The binding affinity of HI313 was measured by flow cytometry; suppression of NB4 cell line proliferation induced by HI313 was measured by MTS; effects of HI313 on cell cycle were assessed by flow cytometry; AML cell differentiation was assessed by detecting cell surface markers CD11b, CD14 and CD15. The results show that anti-CD44 antibody HI313 has relative high affinity to cells both high and low expression of CD44 and effectively suppressed the proliferation of NB4 cell line through blocking of cell cycle progress at G0/G1 phase. Furthermore, HI313 antibody can induce differentiation of cancer cells from AML patients. In conclusion, CD44 is a valid target for AML treatment and HI313 monoclonal antibody is a good candidate for therapeutic antibody development. |
| Keywords: | AML |
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