Expression of a bispecific dsFv–dsFv′ antibody fragment in Escherichia coli

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.