Abstract
Using somatic cell fusion, we produced a bispecific monoclonal antibody with affinity for both fibrin and t-PA. This bispecific MoAb was made with a view to enhancing the efficacy of t-PA in thrombolytic therapy, since the bispecific MoAb increases the binding affinity of t-PA for fibrin, and may simultaneously decrease the clearance rate of t-PA in vivo. In vitro tests show that, in the presence of the bispecific MoAb, a ten-to twentyfold lower concentration of t-PA was needed to obtain the same amount of t-PA binding to fibrin coated wells, as with t-PA alone. The second possible effect of the bispecific MoAb, i.e. the increased half-life of t-PA in vivo, is under investigation.
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References
Cohen, D., Lijnen, H.R., Todd, P.A. and Goa, K.L. (1989) ‘Tissue-Type Plasminogen Activator. A Review of its Pharmacology and Therapeutic Use as a Thrombolytic Agent’, Drugs 38, 346–388.
Krause, J. (1988) ‘Catabolism of Tissue-Type Plasminogen Activator (t-PA), its Mutants and Hybrids’, Fibrinolysis 2, 133–142.
Kruithof, E.K.O., Tran-Tchang, C., Ransijn, A. and Bachmann, F. (1984) ‘Demonstration of a Fast-Acting Inhibitor of Plasminogen Activators in Human Plasma’, Blood 64, 907–913.
Doolittle, R.F (1981) ‘Fibrinogen and Fibrin’, Sci. Am. 245, 92–101.
Niewiarowski, S., Sonyl, A.F. and Gillies, P. (1973) ‘Plasmin-Induced Platelet Aggregation and Platelet Release Reaction. Effects on Hemostasis’, J. Clin. Invest. 52, 1647–1659.
Bennet, W.R., Yawn, D.H., Migliove, P.J., Young, J.B., Pratt, C.M., Raizner, A.E., Roberts, R. and Bolli, R. (1987) ‘Activation of the Complement System by Recombinant Tissue Plasminogen Activator’, J. Am. Col. Cardiol. 10, 627–633.
Cohen, D. (1988) ‘Fibrin Specific Thrombolytic Therapy’, Thromb. Res. sup VIII, 3–14.
Bode, C., Matsueda, G.R., Hui, K.Y. and Haber, E. (1985) ‘Antibody-Directed Urokinase: A Specific Fibrinolytic Agent’, Science 229, 765–767.
Schaub, R.G. and Humphrey, W.R. (1989) ‘In Vivo Fibrinolytic Activity of a Tissue-Type Plasminogen Activator (t-PA) Mutant in a Feline Model of Arterial Thrombosis’, Blood 74 suppl. I, abstr. 364.
Bang, N.U. (1989) ‘Tissue-Type Plasminogen Activator Mutants’, Circulation 79, 1391–1392.
Glennie, M.J., Brennand, D.M., Bryden, F., McBride, H.M., Stirpe, F., Worth, A.A.T. and Stevenson, G.T. (1988) ‘Bispecific F(AB’γ)2 Antibody for the Delivery of Saporin in the Treatment of Lymphoma’, J. Immunol. 141, 3662–3670.
Runge, M.S., Quertermouse, T, Matsueda, G.R. and Haber, E. (1988) ‘Increasing selectivity of PLasminogen Activators with Antibodies’, J. Clin. Res. 36, 501–506.
Tsukada, Y., Ohkawa, K., Hibi, N., Tsuzuki, K., Oguma, K. and Satoh, H. (1988) ‘The Effect of Bispecific Monoclonal Antibody Recognizing Both Hepatoma Specific Membrane Glycoprotein and Anthracyclin Drugs on the Metastatic Growth of Hepatoma AH66’, Cancer Biochem. Biophys. 10, 247–256.
Webb, K., Ware, J.L., Parks, S.F., Walther, P.J. and Paulson, D.F. (1985) ‘Evidence for a Novel Hybrid Immunotoxin Recognizing Ricin A-Chain by One Antigen-Combining Site and a Prostate-Restricted Antigen by the Remaining Antigen-Combining Site: Potential For Immunotherapy’, Cancer Treatment Reports 69, 663–672.
Milstein, C. and Cuello, A.C. (1983) ‘Hybrid Hybridomas and Their Use in Immunohistochemistry’, Nature 305, 537–540.
Wasser, M.N.J.M, Koppert, P.W., Arndt, J.W., Emeis, J.J., Feitsma, R.I.J., Pauwels, E.K.J. and Nieuwenhuizen, W. 1989 ‘An Antifibrin Monoclonal Antibody Useful in Immuniscintigraphic Detection of Thrombi, Blood 74, 708–714.
Bos, R. ‘manuscript in preparation’.
Nelson, JA., Carpenter, J.W., Rose, L.M. and Adamson, D.J. (1975) ‘Mechanisms of Action of 6-Thioguanine, 6-Mercaptopurine, and 8-Azaguanine’, Cancer Res. 35, 2872–2878.
Otter, M., personal communications.
Koppert, P.W., Huijsman, C.G.M., Nieuwenhuizen, W. (1985) ‘A Monoclonal Antibody, Specific for Human Fibrinogen, Fibrinopeptide A-Containing Fragments and Not Reacting With Free Fibrinopeptide A’, Blood 66, 503–507.
Westerwoud, R.J. (1984) ‘Improved Fusion Methods. IV. Technical Aspects’, J. Immunol. Meth. 77, 181–196.
Ey, P.L., Prowse, S.J. and Jenkin, C.R. (1978) ‘Isolation of Pure IgG1, IgG2a and IgG2b Immunoglobulin from Mouse Serum Using Protein A-Sepharose’, Immunochemistry 15, 429–436.
Verheijen, J.H., De Jong, Y.F. and Chang, G.T.C. (1985) ‘Quantative Analysis of the Composition of Mixtures of One-Chain and Two-Cain Tissue-Type Plasminogen Activator With a Spectre-photometric Method’, Thromb. Res. 39, 281–288)
Home, C., Klein, M. Polidoulis, I, and Dorrington, K.J. (1982) ‘Noncovalent Association of Heavy and Light Chains of Human Immunoglobulins’, J. Immunol. 129, 660–665.
Suresh Cuello and Milstein (1986) ‘Advantages of Bispecific Hybridomas in One-Step Immunocytochemistry and Immunoassays’, Proc. Natl. Acad. Sci. USA 83, 7989–7993.
Bos, R., Van Den Berg, E. and Nieuwenhuizen, W. (1990) ‘A Method for the Transformation of Hybridoma Cell Lines With Improved Efficiency: Its Use In the Production of Bispecific Monoclonal Antibodies’, Biotherapeutics, this issue.
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Bos, R., Otter, M., Nieuwenhuizen, W. (1990). Enhanced Binding of t-PA to Fibrin Using Bispecific Monoclonal Antibodies. In: Crommelin, D.J.A., Schellekens, H. (eds) From Clone to Clinic. Developments in Biotherapy, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-3780-5_20
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DOI: https://doi.org/10.1007/978-94-011-3780-5_20
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