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Retargeting serum immunoglobulin with bispecific diabodies

Nature Biotechnology volume 15, pages 632–636 (1997)Cite this article

Abstract

Monospecific antibody fragments produced in bacteria lack the Fc portion of antibodies, and are therefore unable to recruit natural effector functions. We describe the use of a bispecific antibody fragment (diabody) to recruit the whole spectrum of antibody effector functions by retargeting serum immunoglobulin (Ig). One arm of the diabody was directed against the target antigen, and the other against the serum Ig. The bispecific diabodies were able to recruit complement, induce mononuclear phagocyte respiratory burst and phagocytosis, and promote synergistic cytotoxicity towards colon carcinoma cells in conjunction with CD8+ T-cells. Further, by virtue of binding to serum Ig their half-life (β-phase) was increased fivefold compared to a control diabody of the same molecular weight. Such bispecific diabodies may provide an attractive alternative to monoclonal antibodies for serotherapy.

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Author notes

  1. Philipp Holliger: Corresponding author (e-mail: phi@mrc-lmb.cam.ac.uk)

Authors and Affiliations

  1. MRC Centre for Protein Engineering, Hills Rd., Cambridge, CB2 2QH, UK

    Philipp Holliger & Greg Winter

  2. University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Rd., Cambridge, CB22QQ, UK

    Mark Wing

  3. Department of Immunology University of Birmingham, The Medical School, Edgbaston, Birmingham, Bl5 2TT, UK

    John D. Pound

  4. Klinik I für Innere Medizin, Universität zu Köln, J. Stelzmanstr. 9, 50931, Cologne, Germany

    Heribert Bohlen

  5. MRC Laboratory for Molecular Biology, Hills Rd., Cambridge, CB2 2QH, UK

    Greg Winter

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  3. John D. Pound
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  4. Heribert Bohlen
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  5. Greg Winter
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Holliger, P., Wing, M., Pound, J. et al. Retargeting serum immunoglobulin with bispecific diabodies. Nat Biotechnol 15, 632–636 (1997). https://doi.org/10.1038/nbt0797-632

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