A dimeric bispecific miniantibody combines two specificities with avidity.
Bispecific antibodies extend the capabilities of nature and might be applied in immunotherapy and biotechnology. By fusing the gene of a single-chain Fv (scFv) fragment to a helical dimerization domain, followed by a second scFv fragment of different specificity, we were able to express a functional protein in E. coli, which is bispecific and has two valencies for each specificity. The dimeric bispecific (DiBi) miniantibody preserves the natural avidity of antibodies in a very small-sized molecule of only 120 kDa. The generality of the principle was shown with a scFv fragment binding the EGF-receptor (named scFv 425) in three combinations with scFv fragments either directed against CD2 (ACID2.M1), phosphorylcholine (McPC603) or fluorescein (FITC-E2). Binding was analyzed by sandwich surface plasmon resonance biosensor (BIAcore) measurements.
Müller
K M
KM
Biochemisches Institut, Universität Zürich, Switzerland.
Arndt
K M
KM
Plückthun
A
A
D000595:Amino Acid Sequence; D018033:Antibodies, Bispecific / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D018801:CD2 Antigens / Q000276:immunology; D019281:Dimerization; D066246:ErbB Receptors / Q000276:immunology; D019793:Fluorescein; D006241:Haptens / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D057127:Single-Chain Antibodies
D018033:Antibodies, Bispecific; D018801:CD2 Antigens; D006241:Haptens; D007128:Immunoglobulin Fragments; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies; C055966:immunoglobulin Fv; C114035:scFv 425; D010767:Phosphorylcholine; D066246:ErbB Receptors; D019793:Fluorescein