The making of bispecific antibodies
Top Cited Papers
Open Access
- 14 December 2016
- journal article
- review article
- Published by Informa UK Limited in mAbs
- Vol. 9 (2), 182-212
- https://doi.org/10.1080/19420862.2016.1268307
Abstract
During the past two decades we have seen a phenomenal evolution of bispecific antibodies for therapeutic applications. The ‘zoo’ of bispecific antibodies is populated by many different species, comprising around 100 different formats, including small molecules composed solely of the antigen-binding sites of two antibodies, molecules with an IgG structure, and large complex molecules composed of different antigen-binding moieties often combined with dimerization modules. The application of sophisticated molecular design and genetic engineering has solved many of the technical problems associated with the formation of bispecific antibodies such as stability, solubility and other parameters that confer drug properties. These parameters may be summarized under the term ‘developability’. In addition, different ‘target product profiles’, i.e., desired features of the bispecific antibody to be generated, mandates the need for access to a diverse panel of formats. These may vary in size, arrangement, valencies, flexibility and geometry of their binding modules, as well as in their distribution and pharmacokinetic properties. There is not ‘one best format’ for generating bispecific antibodies, and no single format is suitable for all, or even most of, the desired applications. Instead, the bispecific formats collectively serve as a valuable source of diversity that can be applied to the development of therapeutics for various indications. Here, a comprehensive overview of the different bispecific antibody formats is provided.Keywords
This publication has 290 references indexed in Scilit:
- Application of bispecific antibody against antigen and hapten for immunodetection and immunopurificationExperimental & Molecular Medicine, 2013
- Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchangeProceedings of the National Academy of Sciences of the United States of America, 2013
- Bispecific digoxigenin-binding antibodies for targeted payload deliveryProceedings of the National Academy of Sciences of the United States of America, 2011
- Chemical generation of bispecific antibodiesProceedings of the National Academy of Sciences of the United States of America, 2010
- Development of a Two-part Strategy to Identify a Therapeutic Human Bispecific Antibody That Inhibits IgE Receptor SignalingPublished by Elsevier BV ,2010
- Enhancing Antibody Fc Heterodimer Formation through Electrostatic Steering EffectsPublished by Elsevier BV ,2010
- Recombinant Bispecific Monoclonal Antibodies Prepared by the Dock-and-Lock Strategy for Pretargeted RadioimmunotherapySeminars in Nuclear Medicine, 2010
- Pharmacokinetics and Brain Uptake of a Genetically Engineered Bifunctional Fusion Antibody Targeting the Mouse Transferrin ReceptorMolecular Pharmaceutics, 2009
- Combinatorial surrobody librariesProceedings of the National Academy of Sciences of the United States of America, 2008
- Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targetingProceedings of the National Academy of Sciences of the United States of America, 2006