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Title: Identification of functional synergism between monoclonal antibodies. Application to the enhancement of plasminogen activator inhibitor-1 neutralizing effects
Authors: Ngo, Thu Hoa
Debrock, Sophie
Declerck, Paul # ×
Issue Date: Oct-1997
Publisher: Elsevier science bv
Series Title: FEBS Letters vol:416 issue:3 pages:373-376
Abstract: The serpin plasminogen activator inhibitor-1 (PAI-1), an important risk factor for thrombotic disease can be neutralized by distinct mechanisms, We hypothesized that the combination of two compounds, with PAI-1 neutralizing properties based on different mechanisms, may result in a synergistic effect, Therefore, seven monoclonal antibodies with PAI-1 neutralizing properties were pairwise evaluated for the possible presence of synergistic or antagonistic effects, Out of 21 combinations, three particular combinations, i.e. MA-33H1/MA-33B8, MA-33B8/MA-7D4B7, and MA-7D4B7/MA-33H1 exhibited strong synergistic effects in comparison,vith their properties when evaluated individually, The observed synergism resulted in a maximum enhancement between 2- and 5-fold (P < 0.05, vs, theoretically expected effect calculated based on additive effects), Strikingly, synergism was only observed between monoclonal antibodies directed against different epitopes and with different molecular mechanisms of PAI-1 neutralization, This phenomenon of synergism opens new perspectives in the design of therapeutic or preventive strategies aimed at enhancing endogenous fibrinolysis through modulation of PAI-1 activity. (C) 1997 Federation of European Biochemical Societies.
ISSN: 0014-5793
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Pharmaceutical Biology (-)
Assisted Reproductive Technology Laboratory (-)
× corresponding author
# (joint) last author

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