A dimeric bispecific miniantibody combines two specificities with avidity

FEBS Letters

Müller, Kristian M.¹  Arndt, Katja M.¹  Plückthun, Andreas¹ 

[1] Biochemisches Institut, Universität Zürich, Winterthurerstr. 190, CH-8050 Zürich, Switzerland

关键词: Protein design;    Dimerization domain;    Bispecific antibody;    scFv fragment;    425;    anti-EGF-receptor scFv;    dhlx;    helix-turn-helix dimerization domain;    DiBi;    dimeric bispecific;    EGF-R;    epidermal growth factor receptor;    FITC-E2;    anti-fluorescein scFv;    IMAC;    immobilized metal ion affinity chromatography;    PC;    phosphorylcholine;    RU;    resonance units;    M1;    anti-CD2 scFv;    scFv;    single-chain Fv fragment of an antibody;   

DOI  :  10.1016/S0014-5793(98)00829-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown