Complement recruitment using bispecific diabodies.
We describe the engineering of antibody fragments produced in bacteria for recruitment of complement effector functions. From a phage display repertoire we isolated human antibody fragments directed against complement C1q, and linked these to lysozyme-specific antibody fragments, creating bispecific antibodies (diabodies). One diabody was able to recruit C1q, resulting in efficient lysis of lysozyme-coated sheep erythrocytes, and also induced rosette-formation of erythrocytes with human monocytes and phagocytosis after phorbol ester stimulation. These diabodies may have therapeutic applications requiring the activation of complement.
Kontermann
R E
RE
MRC Centre for Protein Engineering, Cambridge, UK. rek@imt.uni-marburg.de
Wing
M G
MG
Winter
G
G
D000818:Animals; D018033:Antibodies, Bispecific / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001709:Biotechnology; D003167:Complement Activation; D015922:Complement C1q / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000276:immunology; D009113:Muramidase / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D015202:Protein Engineering
D018033:Antibodies, Bispecific; D009838:Oligodeoxyribonucleotides; D015922:Complement C1q; D003165:Complement System Proteins; D009113:Muramidase