The potential improvement of thrombolytic therapy by targeting with bispecific monoclonal antibodies: Why they are used and how they are made
article
The generation of the proteolytic enzyme plasmin from its inactive precursor plasminogen, mediated by so called plasminogen activators, is the essential step in thrombolytic therapy. Plasmin is responsible for the degradation of the insoluble fibrin, the major component of a thrombus, to soluble fibrin degradation products. So far, the use of the more recently developed thrombolytic agents single-chain urokinase-type plasminogen activator (scu-PA) and tissue-type plasminogen activator (t-PA) were disappointing, mainly due to some of their negative properties in vivo, i.e., rapid inhibition and/or hepatic clearance. Besides some background information on the haemostatic balance; t-PA and scu-PA structure; and mechanisms of action, we here review some reported attempts to improve on these agents for thrombolytic therapy following various strategies. One of the more potential strategies, antibody-targeted thrombolytic therapy using bispecific monoclonal antibodies, is discussed somewhat more extensively, as are the several procedures that can be followed for bispecific antibody preparation. Chemicals/CAS: Antibodies, Monoclonal; Fibrinolytic Agents; Tissue Plasminogen Activator, EC 3.4.21.68; Urinary Plasminogen Activator, EC 3.4.21.73
Topics
anistreplasefibrinolytic agentmonoclonal antibodyprourokinasestreptokinasetissue plasminogen activatorurokinaseblood clot lysisblood clottingcell linedrug targetinghumanhybridomanonhumanreviewAnimalAntibodies, MonoclonalFibrinolytic AgentsHumanMutationThrombolytic TherapyTissue Plasminogen ActivatorUrinary Plasminogen Activator
TNO Identifier
231955
ISSN
0921299X
Source
Biotherapy, 5(3), pp. 187-199.
Pages
187-199
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