In vitro studies of a bispecific monoclonal antibody antithrombotic conjugate [ATC(3)]

Ranjit S. More; Malcolm J. Underwood; Michael J. Brack; Serena Pringle; David P. de Bono; Anthony H. Gershlick

doi:10.1007/BF02043623

International Journal of Angiology, Table of Contents

Int J Angiol 1995; 4(2): 83-87
DOI: 10.1007/BF02043623

Original Articles

In vitro studies of a bispecific monoclonal antibody antithrombotic conjugate [ATC(3)]

Ranjit S. More, Malcolm J. Underwood, Michael J. Brack, Serena Pringle, David P. de Bono, Anthony H. Gershlick

Academic Department of Cardiology, Clinical Sciences Wing, Glenfield General Hospital, Leicester, LE3 9QP, UK

Presented at the 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993R.S.M., M.J.B., M.U., and S.P. are supported by grants from the British Heart Foundation

Abstract

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Abstract

We assessed whether chemical conjugation of a monoclonal antibody (M735) against platelet glycoprotein IIb/IIIa receptors to urokinase and to a monoclonal antibody which binds to damaged endothelium (P14G11) resulted in enhanced inhibition of platelet aggregation with maintenance of localizing features (to damaged endothelium). Conjugation of M735 (an IgM monoclonal antibody) to urokinase and P14G11 (an IgG2a monoclonal antibody) was carried out using SPDP [N-Succinimidyl-3-(2-pyridyldithio)-propionate] as the cross-linking reagent. The resulting triple conjugate [ATC(3)] had fibrinolytic activity and retained platelet and damaged endothelium localizing features. Enhanced inhibition of platelet aggregation (induced by either adenosine diphosphate (ADP), collagen, or thrombin) was observed compared with both an unconjugated mixture of the three individual components and to the M735-urokinase conjugate. We conclude that it is possible to produce a bimonoclonal antibody-urokinase agent which has both potent antiplatelet aggregatory effects and additional targeting or localizing features.

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