title: Progress in overcoming the chain association issue in bispecific heterodimeric IgG antibodies.
abstract: The development of bispecific antibodies has attracted substantial interest, and many different formats have been described. Those specifically containing an Fc part are mostly tetravalent, such as stabilized IgG-scFv fusions or dual-variable domain (DVD) IgGs. However, although they exhibit IgG-like properties and technical developability, these formats differ in size and geometry from classical IgG antibodies. Thus, considerable efforts focus on bispecific heterodimeric IgG antibodies that more closely mimic natural IgG molecules. The inherent chain association problem encountered when producing bispecific heterodimeric IgG antibodies can be overcome by several methods. While technologies like knobs-into-holes (KiH) combined with a common light chain or the CrossMab technology enforce the correct chain association, other approaches, e.g., the dual-acting Fab (DAF) IgGs, do not rely on a heterodimeric Fc part. This review discusses the state of the art in bispecific heterodimeric IgG antibodies, with an emphasis on recent progress.
authors.affiliation: Discovery Oncology, Roche Pharma Research and Early Development pRED, Roche Glycart AG, Schlieren, Switzerland. christian.klein.ck1@roche.com
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Claudio
authors.initials: C
authors.lastname: Sustmann
authors.forename: Markus
authors.initials: M
authors.lastname: Thomas
authors.forename: Kay
authors.initials: K
authors.lastname: Stubenrauch
authors.forename: Rebecca
authors.initials: R
authors.lastname: Croasdale
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schanzer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brinkmann
authors.forename: Hubert
authors.initials: H
authors.lastname: Kettenberger
authors.forename: Jörg T
authors.initials: JT
authors.lastname: Regula
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000915:Antibody Affinity; D015195:Drug Design; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D011485:Protein Binding; D015202:Protein Engineering; D055503:Protein Multimerization; D057127:Single-Chain Antibodies / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D018033:Antibodies, Bispecific; D057127:Single-Chain Antibodies