Monoclonal antibodies to tissue-type plasminogen activator which prolong its clearance in vivo.
Three murine monoclonal antibodies to tissue-type plasminogen activator (t-PA) were evaluated for their effects on the binding of iodinated t-PA to cultured human hepatoma cells (Hep G2), and on extending the half-life of t-PA injected into rabbits. Two of the antibodies, AE5 and EG2, significantly inhibited t-PA binding in vitro, and extended the in vivo half-life of t-PA four to five-fold. A third antibody, BA10, which had a much smaller inhibitory effect on t-PA binding, had no influence in extending t-PA's half-life. MOPC-21, a control antibody not directed to t-PA, had no effect on either test. Our results are the first to correlate different compounds' effects on t-PA binding with their ability to retard t-PA clearance in vivo, and provide additional evidence for the importance of a liver cell receptor in the t-PA clearance process.
Reilly
T M
TM
E.I. du Pont de Nemours and Company, Medical Products Department, Wilmington, Delaware 19880-0400.
Knabb
R M
RM
Chiu
A T
AT
Bradfute
D L
DL
Timmermans
P B
PB
D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008113:Liver Neoplasms; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D010959:Tissue Plasminogen Activator