[抗Pgp/抗CD3双抗体介导的对耐药白血病细胞的特异性靶向细胞毒性作用]
[Specific targeting cytotoxicity to resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody].
作者信息
Gao Ying-dai, Xiong Dong-sheng, Yang Ming, Xu Yuan-fu, Shao Xiao-feng, Peng Hui, Fan Dong-mei, Yang Chun-zheng
机构信息
State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS & PUMC, Tianjin 300020, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2005 Jun;26(6):342-4.
OBJECTIVE
To study the specific targeting cytotoxicity to drug-resistant leukemia cells mediated by anti-Pgp/anti-CD3 diabody.
METHODS
The diabody was purified by affinity chromatography and identified by SDS-PAGE and FACS. The effect of the anti-Pgp/anti-CD3 diabody mediated lysis of Pgp-expressing tumor cells was assayed by human leukemia nude mice xenograft model in vivo.
RESULTS
The diabody was produced in E.coli in a soluble functional form and could bind both Jurkat cells (CD3(+)) and K562/A02 cells (Pgp(+)). The binding rates were 86.25% and 86.26%, respectively. It could inhibit tumor growth by 98.57% and prolonged the survival of mice bearing xenografted K562/A02 cells.
CONCLUSION
The diabody was proved to be a potent agent for mediating T lymphocyte cytotoxicity to lyse Pgp expressing tumor cells in vitro and in vivo.
目的
研究抗Pgp/抗CD3双抗体介导的对耐药白血病细胞的特异性靶向细胞毒性。
方法
通过亲和层析纯化双抗体，并经SDS-PAGE和流式细胞术鉴定。采用人白血病裸鼠异种移植模型在体内检测抗Pgp/抗CD3双抗体介导的对表达Pgp的肿瘤细胞的裂解作用。
结果
双抗体在大肠杆菌中以可溶性功能形式产生，能与Jurkat细胞（CD3(+)）和K562/A02细胞（Pgp(+)）结合，结合率分别为86.25%和86.26%。它能抑制肿瘤生长98.57%，并延长荷K562/A02细胞异种移植瘤小鼠的生存期。
结论
双抗体被证明是一种有效的药物，可在体外和体内介导T淋巴细胞细胞毒性以裂解表达Pgp的肿瘤细胞。
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