A bispecific antibody enhances the fibrinolytic potency of single-chain urokinase.
A monoclonal antibody specific for an epitope at the amino terminus of the beta chain of fibrin and a monoclonal antibody that binds both one- and two-chain high molecular weight urokinase were chemically cross-linked [using N-succinimidyl 3-(2-pyridyldithio)propionate and 2-iminothiolane]. The chemically modified material was heterogeneous, ranging in molecular size from tetramers to monomers and containing the two antibodies in various ratios. Nevertheless, fractions of a molecular size larger than a monomer were capable of binding fibrin and urokinase simultaneously in a radioimmunoassay. These fractions also enhanced fibrinolysis by high molecular weight single-chain urokinase (scuPA) by 50-fold and plasma clot lysis by 5-fold. Whereas scuPA significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, scuPA in association with the bispecific antibody did not.
Charpie
J R
JR
Massachusetts General Hospital, Boston 02114.
Runge
M S
MS
Matsueda
G R
GR
Haber
E
E
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D000939:Epitopes / Q000276:immunology; D005337:Fibrin / Q000276:immunology* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D010960:Plasminogen Activators / Q000276:immunology / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D005337:Fibrin; D005340:Fibrinogen; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator