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一种新型重组抗体导向溶栓剂的体外溶栓研究 |
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万海英 刘征辉 顾津明 朱明清 李佩霞 阮长耿
摘 要 目的：探讨一种新型重组融合基因抗体导向溶栓剂SZ51Hu-scuPA的体外溶栓效力。方法：通过转瓶扩大生产获得的大量 基因重组融合蛋白SZ51Hu-scuPA，通过抗体竞争结合实验确定融合蛋白的抗体亲和力；进 而与尿激酶进行不同浓度血小板血浆凝块体外溶栓比较。结果：该融合 蛋白体外纤溶活性为39 000 U/mg；其抗体亲和力是鼠源性单抗的67%；体外溶栓效力较uPA 提高4.1～8.4倍。结论：体外溶栓结果证明，融合蛋白SZ51Hu-scuPA 既兼有与人活化血小板结合特性又有纤溶酶原激活剂特性的双功能分子，是一种新型的抗体 导向溶栓剂。
关键词 活化血小板 单抗 单链尿激酶 基因表达 导向溶栓
中国图书分类号 R73-354
Study on thrombolysis of a new recombinant ant ibody-targeted plasminogen activator in vitro
WAN Hai-Ying LIU Zheng-Hui GU Jing-Ming
（Jiangsu Institute of Hematology,the First Affiliated Hospital of Suzhou Medical College, Suzhou 215006）
Abstract Objective：To compare the thrombolytic propertie s in vitro between urokinase(uPA) and the recombinant chimeric plasminogen activ a tor SZ51Hu-scuPA,which was composed of a humanized monoclonal antibody SZ51(SZ5 1 Hu) specifically against activated human platelet and a single-chain urokinase( scuPA).Methods:The fusion protein SZ51Hu-scuPA was produc ed from the supernatant of a stable myeloma cell line growing in spinner flask,a nd then purified by chromatography on a GAH IgG-Sepharose 4B affinity column.Th e binding capacity to activted human platelet of purified fusion protein SZ51Hu -scuPA was obtained by antibody competitive binding assay.The thrombolytic acti vity was determined by lysis of 125I-fibrin-labelled human plasma cl ots. Results:SZ51Hu-scuPA affinity was 67% of the SZ-51M an d the fibrinolytic activity was 39 000 U/mg. The lysis of the clots by SZ51Hu-s c uPA was 4.1～8.4 fold more potent than uPA.Conclusion:Th e fusion protein SZ51Hu-scuPA was more competent to dissolve platelet clots than uPA and it was a new recombinant antibody-targeted plasminogen activator in vit ro.
Key words Activated platelets Monoclonal antibody Si ngle-chain urokinase Gene expression Targeting thrombolysis
抗人活化血小板GMP-140单抗SZ-51(SZ-51M)，经放射性核素99mTc标记后(99mTc-SZ51)不仅在实验性狗股动、静脉血栓模型中，而[1] [2] 下一页
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