Retargeting serum immunoglobulin with bispecific diabodies.
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 (beta-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.
Holliger
P
P
MRC Centre for Protein Engineering, Cambridge, UK. ph1@mrc-lmb.cam.ac.uk
Wing
M
M
Pound
J D
JD
Bohlen
H
H
Winter
G
G
D000818:Animals; D018033:Antibodies, Bispecific / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D000941:Antigens; D001483:Base Sequence; D001709:Biotechnology; D003165:Complement System Proteins / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D006207:Half-Life; D006801:Humans; D007116:Immunization, Passive; D007136:Immunoglobulins / Q000097:blood*; D009113:Muramidase / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000941:Antigens; D017931:DNA Primers; D007136:Immunoglobulins; D017452:Receptors, IgG; D003165:Complement System Proteins; D009113:Muramidase