Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma1 Fc or CH3 region

FEBS Lett. 1999 Jul 2;454(1-2):90-4. doi: 10.1016/s0014-5793(99)00782-6.

Abstract

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.

MeSH terms

  • Antibodies, Bispecific / immunology*
  • Antibody Affinity
  • Cell Line
  • Chromatography, Gel
  • Dose-Response Relationship, Immunologic
  • Humans
  • Immunoglobulin Constant Regions / immunology*
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulins / immunology*
  • Models, Biological

Substances

  • Antibodies, Bispecific
  • Immunoglobulin Constant Regions
  • Immunoglobulin Fc Fragments
  • Immunoglobulins