抗Pgp/抗CD3双特异双链抗体的生物学活性研究 |
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引用本文: | 高瀛岱,熊冬生,许元富,杨铭,彭晖,邵晓枫,刘汉芝,杨纯正. 抗Pgp/抗CD3双特异双链抗体的生物学活性研究[J]. 中华微生物学和免疫学杂志, 2004, 24(5): 352-355 |
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作者姓名: | 高瀛岱 熊冬生 许元富 杨铭 彭晖 邵晓枫 刘汉芝 杨纯正 |
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作者单位: | 300020,天津,中国协和医科大学,中国医学科学院血液学研究所实验血液学国家重点实验室 |
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基金项目: | 国家高科技研究发展专项经费资助项目(2 0 0 2AA2Z3 46D) |
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摘 要: | 目的 研究抗Pgp 抗CD3双特异双链抗体介导的特异性靶向杀伤活性。方法 采用亲和层析法分离纯化本室构建的抗Pgp 抗CD3双特异双链抗体可溶性表达产物 ,并用SDS PAGE、Westernblot及抗活细胞间接免疫荧光法鉴定纯化产物 ;采用51 Cr释放试验测定其介导的体外靶向杀伤活性。结果 纯化的抗Pgp 抗CD3双特异双链抗体具有与Jurkat细胞 (CD3 )和K5 6 2 A0 2 (Pgp )细胞结合的活性 ;抗Pgp 抗CD3双特异双链抗体具有介导激活的T淋巴细胞杀伤Pgp表达阳性的耐药肿瘤细胞的作用 ,杀伤作用的强弱显示出效靶比和剂量依赖关系 ,且可被CD3ScFv或PgpScFv特异性的阻断。结论 抗Pgp 抗CD3微型双功能抗体有望成为治疗耐药肿瘤 ,特别是肿瘤残留灶和微小转移灶的治疗的一种新策略。
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关 键 词: | Pgp CD3 基因工程抗体 双特异性抗体 |
修稿时间: | 2003-11-07 |
Biological activity of anti-CD3/anti-Pgp diabody |
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Abstract: | Objective To study the biological activity of anti-CD3/anti-Pgp diabody. Methods The anti-CD3/anti-Pgp diabody was purified by affinity chromatography and analyzed by Western blot and size exclusion chromatography;its antigen-binding activity was examined by FACS. Its biological activity was examined by 51 Cr release test. Results The anti-CD3/anti-Pgp diabody can bind to Jurkat cells (CD3 ) and K562/A02 cells(Pgp ). In the presence of activated human peripheral blood lymphocytes (PBL), the diabody mediates effectively the lysis of the Pgp-overexpressing human leukemia K562/A02, but is much less potent in mediating the lysis of the parent K562. Conclusion The biological activity experiments demonstrated that the diabody the anti-Pgp/anti-CD3 diabody may have great potential in the treatment of MDR cancers. |
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Keywords: | Pgp CD3 Engineering antibody Bispecific antibody |
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