Design and production of novel tetravalent bispecific antibodies

Nat Biotechnol. 1997 Feb;15(2):159-63. doi: 10.1038/nbt0297-159.


We have produced novel bispecific antibodies by fusing the DNA encoding a single chain antibody (ScFv) after the C terminus (CH3-ScFv) or after the hinge (Hinge-ScFv) with an antibody of a different specificity. The fusion protein is expressed by gene transfection in the context of a murine variable region. Transfectomas secrete a homogeneous population of the recombinant antibody with two different specificities, one at the N terminus (anti-dextran) and one at the C terminus (anti-dansyl). The CH3-ScFv antibody, which maintains the constant region of human IgG3, has some of the associated effector functions such as long half-life and Fc receptor binding. The Hinge-ScFv antibody which lacks the CH2 and CH3 domains has no known effector functions.

MeSH terms

  • Animals
  • Antibodies, Bispecific / biosynthesis*
  • Antibodies, Bispecific / chemistry*
  • Antibodies, Bispecific / isolation & purification
  • Antibody Affinity
  • Chromatography, Gel
  • Dansyl Compounds
  • Drug Design
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin Constant Regions / biosynthesis*
  • Immunoglobulin Constant Regions / chemistry
  • Immunoglobulin G / biosynthesis*
  • Immunoglobulin G / chemistry
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Kinetics
  • Ligands
  • Mice
  • Multiple Myeloma
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Transfection


  • Antibodies, Bispecific
  • Dansyl Compounds
  • Immunoglobulin Constant Regions
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Ligands
  • Recombinant Fusion Proteins