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Enhanced Fibrinolysis by a Bispecific Monoclonal Antibody Reactive to Fibrin and Tissue Plasminogen Activator

Bio/Technology volume 7, pages 1163–1167 (1989)Cite this article

Abstract

We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (bs mAb) by fusing a hybridoma secreting an anti-tissue plasminogen activator (tPA) mAb with a hybridoma secreting a mAb that binds to human fibrin but not to fibrinogen. The bs mAb, reactive to both fibrin and tPA, was purified by affinity chromatography employing antigen-coupled columns and characterized by SDS-PAGE, a fibrin-binding assay, an amidolytic assay, a fibrinolytic assay and a thrombolytic assay. The immunochemical conjugation of tPA and the bs mAb did not impair the catalytic activity of tPA and made it possible to concentrate tPA at fibrin clots. Pretreatment of fibrin with the bs mAb enhanced the fibrin-binding of tPA and subsequent fIbrinolysis. The tPA-bs mAb immunoconjugate exhibited more thrombolytic activity than tPA alone in the rabbit jugular vein model.

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  1. Susumu Iwasa: Corresponding author.

Authors and Affiliations

  1. Biotechnology Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., 17-85 Jusohonmachi 2-chome, Yoaogawa-ku, Osaka, 532, Japan

    Tomofumi Kurokawa, Susumu Iwasa & Atsushi Kakinuma

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  1. Tomofumi Kurokawa
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  2. Susumu Iwasa
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  3. Atsushi Kakinuma
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Kurokawa, T., Iwasa, S. & Kakinuma, A. Enhanced Fibrinolysis by a Bispecific Monoclonal Antibody Reactive to Fibrin and Tissue Plasminogen Activator. Nat Biotechnol 7, 1163–1167 (1989). https://doi.org/10.1038/nbt1189-1163

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