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抗CD3/抗B细胞肿瘤的双功能小抗体的抗肿瘤活性研究

In vitro and in vivo Anti-tumor Activity of Anti-CD3/Anti-B cell Carcinoma Bispecific Antibody

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【作者】 许元富熊冬生杨纯正邵晓枫彭晖范冬梅刘汉芝赖增祖高赢岱朱祯平

【Author】 Xu Yuanfu, Xiong Dongsheng, Yang Chunzheng, Shao Xiaofeng, Peng Hui, Fang Dongmei, Liu Hanzhi, Lai Zhengzu, Gao Yingdai, Zhu Zhenping (The State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS&PUMC, Tianjin 300020)

【机构】 中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室 天津300020天津300020天津300020

【摘要】 为评价已研制的抗CD3/抗B细胞肿瘤 (CD2 0 + )双功能小抗体的生物学活性 ,采用多种实验方法在体内外对其进行研究。结果表明 :该型双功能小抗体能同时与Ju rkat和Daudi细胞结合 ,并交联两种细胞形成玫瑰花环。它与Jurkat(CD3+ )和Daudi细胞 (CD2 0 + )的结合的亲和常数Ka分别为 3.2× 10 8M- 1和 8.9× 10 8M- 1。在体外该抗体能激活并介导T细胞杀伤Daudi细胞。裸鼠体内分布实验结果表明 :该型抗体可在移植瘤部位富集 ;在人B淋巴瘤裸鼠移植瘤腹腔模型中 ,联合人的PBMC和IL 2 ,该抗体可以杀灭人B淋巴瘤细胞 ,明显延长荷瘤裸鼠的生存时间。

【Abstract】 In order to evaluate the biological activity of the anti-CD3/anti-B cell carcinoma(CD20+) bispecific antibody prepared by our lab, lots of experimental methods were used to analyze it both in vitro and in vivo. The results from current research are shown as follows: this kind of engineering anibody could bind to Jurkat cell(CD3+) and Daudi cell(CD20+) simultaneously, and by that way the antibody was capable of cross-linking those two types cells to form cellular resetting, the affinity constant(Ka) of them were 3.2×108M -1 and 8.9×108M -1, respectively. In vitro, the engineering antibody could efficiently activated human T cell to lyse B lymphoma cells in a dose-dependent manner. In vivo, 125I labeled anti-CD3/anti-CD20 antibody localized preferentially in subcutaneously implanted Raji tumor(CD20+) in nude mice, and in a separate study, administered along with IL-2 and T-riched human PBMC, the antibody could recruited T cells to kill B lymphoma cell(CD20+) and inhibited the growth of xenografted human B lymphoma in the nude mice, and significantly prolonged the survival of tumor-bearing nude mice.

【关键词】 双功能抗体CD3CD20B淋巴瘤
【Key words】 Bispecific antibodyMCD3CD20B lymphoma
【基金】 863计划 ( 10 2- 0 9 0 3 - 0 3 );天津自然基金 ( 993 80 3 811)资助项目
  • 【文献出处】 高技术通讯 ,High Technology Letters , 编辑部邮箱 ,2003年08期
  • 【分类号】R73-36
  • 【被引频次】1
  • 【下载频次】38
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