Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma l Fc or CH3 region

Although bispecific IgG molecules have been successfully applied for antibo dy-mediated immunotherapy of tumours, applicability is hampered by the diff iculties associated with their generation. In the present study, me have us ed a bispecific single-chain diabody (scDb) directed against carcinoembryon ic antigen and Escherichia coli beta-galactosidase as a model to generate b ispecific IgG-like antibody molecules. We show that the fusion of this sing le-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin gamma 1 chain results in the expression of dimeric fusion pr oteins exhibiting four functional antigen binding sites with increased func tional affinity, This strategy represents a new and convenient way to gener ate IgG-like multivalent and bispecific molecules that are efficiently secr eted from mammalian cells. (C) 1999 Federation of European Biochemical Soci eties.