Nature Biotechnology
15, 632 - 636 (1997)
doi:10.1038/nbt0797-632
Retargeting serum immunoglobulin with bispecific diabodiesPhilipp Holliger1, *, Mark Wing2, John D. Pound3, Heribert Bohlen4
& Greg Winter1, 5
1MRC Centre for Protein Engineering, Hills Rd., Cambridge CB2 2QH, UK.
2University of Cambridge Neurology Unit, Addenbrooke's Hospital, Hills Rd., Cambridge, CB22QQ, UK.
3Department of Immunology University of Birmingham, The Medical School, Edgbaston, Birmingham Bl5 2TT, UK.
4Klinik I für Innere Medizin, Universität zu Köln, J. Stelzmanstr. 9,50931 Cologne, Germany
5MRC Laboratory for Molecular Biology, Hills Rd., Cambridge CB2 2QH, UK.
*Corresponding author (e-mail: phi@mrc-lmb.cam.ac.uk) 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 ( -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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