[Antibody mediated thrombolysis. A new therapeutic principle].
Thrombosis of a coronary artery is the most common cause of myocardial infarction. Thrombolytic therapy, when instituted timely, has been shown capable of reducing morbidity and mortality. However, the use of presently available thrombolytic agents is associated with a bleeding tendency and efficacy is not optimal. This article reviews one of several lines of investigation that are presently being pursued in order to improve efficacy and specificity of thrombolytic therapy. The chemical conjugation of a fibrin specific monoclonal antibody and urokinase or tissue plasminogen activator results in markedly enhanced thrombolytic potency, both in vitro and in vivo. Specificity of the conjugates is greater than that of the parent plasminogen activators as reflected by conservation of fibrinogen, plasminogen and alpha-2 antiplasmin. A bispecific antibody, with specificity for both, fibrin and tissue plasminogen activator, has the potential of concentrating endogenous tissue plasminogen activator at the site of a thrombus. In the presence of the bispecific antibody, efficacy and specificity of tissue plasminogen activator are markedly enhanced in vitro and in vivo. The tools of molecular biology are presently being applied in order to translate these findings into better thrombolytic therapy.
Bode
C
C
Medizinische Klinik III, Universität Heidelberg.
Kübler
W
W
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D003327:Coronary Disease / Q000628:therapy*; D003328:Coronary Thrombosis / Q000628:therapy*; D005337:Fibrin / Q000276:immunology*; D006801:Humans; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D005337:Fibrin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator
Antikörper-vermittelte Thrombolyse. Ein neues therapeutisches Prinzip.