Developmental Studies on the Treatment of Thrombotic Diseases Using A New Monoclonal Anti-GMP-140 Antibody Specific to Activated Human and Rabbit Platelets and its Modified Bispecific Antibody.

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An anti-GMP-140 monoclonal antibody, 2T60, was developed by immunizing with human thrombin-activated platelets. The antibody recognized also rabbit activated platelets. Since the human platelets obtained from the patients under extracorpuscular circulations such as cardio-pulmonary bypass became to bind more and more 2T60 antibody during the operative processes, this antibody is of great value for diagnosis of thrombotic diseases because it can detect the activated platelets circulating in thrombotic diseases.A monoclonal antibody, UP4-33, bispecific to both GMP-140 and urokinase (UK) was produced by the fusion of the 2T60-producing cells and the splenic cells of the mice immunized with UK. UP4-33 in combination with UK had a higher fibrinolytic activity when added into the clots derived from platelet-rich plasma (PRP) than platelet-poor plasma, suggesting a targetting effect of UP4-33 antibody to activated platelets. ADP-induced platelet aggregation in PRP was more easily deaggregated by UP4-33 in combination with UK than UK alone. In experimental cerebral thrombosis in rabbits that we had previously developed by injection of arachidonic acid (AA) into an internal carotid artery, pretreatment of the animals with both UP4-33 and UK resulted in lower occurrence of cerebral thrombosis than that with UK alone. These results suggest that UP4-33 antibody can be a strong tool for the treatment and protection of thrombotic diseases.