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目的研究抗纤维蛋白-抗尿激酶双特异性单克隆抗体在体内外的溶栓效力。方法通过分泌抗纤维蛋白单抗的杂交瘤细胞(变异株)与尿激酶免疫小鼠的脾细胞融合,获得分泌双特异性单抗(bsMcAbs)杂交-杂交瘤细胞。采用ELISA法检测该bsMcAbs与纤维蛋白和尿激酶的结合力。用131I血浆-血浆凝块溶解率法测定体外溶栓效力。用兔血栓模型测定体内溶栓效力。结果获得8株分泌抗纤维蛋白-抗尿激酶双特异性单抗的杂交-杂交瘤细胞。ELISA实验证明bsMcAbs与纤维蛋白和尿激酶均有很强的结合力。体外溶栓实验证明bsMcAbs可使尿激酶的溶栓效力增强15.5%。体内溶栓实验证明bsMcAbs的溶栓效力为尿激酶的1.6~2.1倍。结论单抗导向溶栓剂具有高度特异性和局部溶栓效力强等优点,值得进一步研究。
Objective To study the thrombolytic efficacy of anti-fibrin-anti-urokinase bispecific monoclonal antibody in vitro and in vivo. Methods The secretory bispecific monoclonal antibody (bsMcAbs) hybridoma cells were obtained by the fusion of anti-fibrin monoclonal antibody-secreting hybridoma cells (mutant) and urokinase-immunized mice spleen cells. The binding of bsMcAbs to fibrin and urokinase was detected by ELISA. In Vitro Thrombolytic Efficacy by 131I Plasma-Plasma Clot Solubility Assay. In vivo thrombolytic efficacy was measured using a rabbit thrombus model. Results Eight hybridoma cells secreting anti-fibrin-anti-urokinase bispecific monoclonal antibodies were obtained. ELISA experiments show that bsMcAbs and fibrin and urokinase have a strong binding force. In vitro thrombolysis experiments showed that bsMcAbs increased the thrombolytic potency of urokinase by 15.5%. In vivo thrombolysis experiments showed that the thrombolytic potency of bsMcAbs was 1.6 to 2.1 times that of urokinase. Conclusion Monoclonal antibody-guided thrombolytic agent has the advantages of high specificity and strong local thrombolytic efficacy, which deserves further study.