Thrombolytic and pharmacokinetic properties of a conjugate of recombinant single-chain urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin in a baboon venous thrombosis model

Circulation
D CollenJ M Stassen

Abstract

Chemical conjugates between recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and a murine monoclonal antibody directed against fragment D-dimer of cross-linked human fibrin (MA-15C5), rscu-PA/MA-15C5, and between rscu-PA and a control monoclonal antibody (MA-1C8), rscu-PA/MA-1C8, were produced by cross-linking with N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). In an in vitro system composed of a [125 I]fibrin-labeled baboon plasma clot immersed in autologous citrated plasma, dose- and time-dependent lysis was obtained with a ratio of the potencies of free and conjugated rscu-PA similar to that in human plasma: 50% lysis in 2 hours required 4.3 micrograms/ml rscu-PA, 1.0 microgram/ml urokinase-type plasminogen activator (u-PA) equivalent rscu-PA/MA-15C5, or 15 micrograms/ml u-PA equivalent rscu-PA/MA-1C8. The thrombolytic and pharmacokinetic properties of rscu-PA and of rscu-PA/MA-15C5 were compared in baboons with a 0.8-1.0 ml [125 I]fibrin-labeled autologous blood clot produced in a femoral vein. Continuous intravenous infusion of these compounds during a 2-hour period resulted in dose- and time-dependent lysis. The thrombolytic potency of rscu-PA/MA-15C5 was 3.0 +/- 0.5 times higher (50% lysis w...Continue Reading

References

Apr 1, 1987·Seminars in Thrombosis and Hemostasis·H R LijnenD C Collen
Apr 1, 1987·Journal of Molecular and Cellular Cardiology·C BodeE Haber
Jun 27, 1983·Annals of the New York Academy of Sciences·P J Gaffney
Mar 1, 1982·The Journal of Clinical Investigation·C KorningerD Collen
May 1, 1963·Clinica Chimica Acta; International Journal of Clinical Chemistry·C VERMYLENM VERSTRAETE

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Citations

Apr 1, 1992·Cardiovascular Drugs and Therapy·M Verstraete
Nov 1, 1993·Cardiovascular Drugs and Therapy·R C Becker
Jan 1, 1993·Biotechnology Advances·H R Lijnen, D Collen
May 1, 1992·Trends in Cardiovascular Medicine·I M LubinM S Runge
Dec 19, 2000·Enzyme and Microbial Technology·P JiangB Ru
Mar 1, 1991·MNA Accent·K Barvels
Dec 1, 1994·Cardiovascular Drugs and Therapy·M Verstraete, H R Lijnen
Dec 4, 1992·Annals of the New York Academy of Sciences·V P Torchilin
Dec 4, 1992·Annals of the New York Academy of Sciences·E HaberM S Runge
Dec 4, 1992·Annals of the New York Academy of Sciences·H R Lijnen, D Collen
Jan 3, 1992·The American Journal of Cardiology·D Collen
Jan 25, 2017·Frontiers of Medicine·Melvin E Klegerman
Jul 1, 1992·Bioconjugate Chemistry·C BodeE Haber
Mar 1, 1991·British Journal of Haematology·H R Lijnen, D Collen
Sep 1, 1991·Progress in Cardiovascular Diseases·D CollenH K Gold

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