Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma1 Fc or CH3 region.
Although bispecific IgG molecules have been successfully applied for antibody-mediated immunotherapy of tumours, applicability is hampered by the difficulties associated with their generation. In the present study, we have used a bispecific single-chain diabody (scDb) directed against carcinoembryonic antigen and Escherichia coli beta-galactosidase as a model to generate bispecific IgG-like antibody molecules. We show that the fusion of this single-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin gamma1 chain results in the expression of dimeric fusion proteins exhibiting four functional antigen binding sites with increased functional affinity. This strategy represents a new and convenient way to generate IgG-like multivalent and bispecific molecules that are efficiently secreted from mammalian cells.
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Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Germany.
Müller
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Kontermann
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D018033:Antibodies, Bispecific / Q000276:immunology*; D000915:Antibody Affinity; D002460:Cell Line; D002850:Chromatography, Gel; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology*; D008954:Models, Biological
D018033:Antibodies, Bispecific; D007127:Immunoglobulin Constant Regions; D007141:Immunoglobulin Fc Fragments; D007136:Immunoglobulins