Monoclonal antibodies to tissue-type plasminogen activator which prolong its clearance in vivo
Reilly, T.M.; Knabb, R.M.; Chiu, A.T.; Bradfute, D.L.; Timmermans, P.B.
Thrombosis and Haemostasis 61(2): 259-261
1989
ISSN/ISBN: 0340-6245 PMID: 2546285 Document Number: 346528
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.