Expression of a bispecific dsFv-dsFv' antibody fragment in Escherichia coli

Protein Eng. 2000 Oct;13(10):725-34. doi: 10.1093/protein/13.10.725.

Abstract

A bispecific disulfide-stabilized Fv antibody fragment (dsFv-dsFv') consisting of two different disulfide-stabilized Fv antibody fragments connected by flexible linker peptides was produced by secretion of three polypeptide chains into the periplasm of Escherichia coli. The dsFv-dsFv' molecules were enriched by immobilized metal affinity chromatography and further purified by anion-exchange chromatography. The recombinant antibody constructs retained the two parental antigen binding specificities and were able to cross-link the two different antigens. The described dsFv-dsFv' design might be of particular value for therapeutic in vivo applications since improved stability is expected to be combined with minimal immunogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / biosynthesis
  • Antibodies, Bispecific / chemistry*
  • Antibodies, Bispecific / isolation & purification
  • Antibody Affinity
  • Disulfides / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / immunology*
  • Genetic Vectors / chemical synthesis
  • Immunoblotting
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / isolation & purification
  • Mice
  • Mutagenesis, Insertional
  • Peptides / chemistry
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / isolation & purification

Substances

  • Antibodies, Bispecific
  • Disulfides
  • Immunoglobulin Variable Region
  • Peptides
  • Recombinant Proteins