A bispecific IgG format containing four independent antigen binding sites

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the variable light (VL) domain in a conventional IgG. VH domains, binding several different types of antigens, were discovered and could be rearranged in any combination, offering a convenient "plug and play" format. The tetra-VH IgGs were found to be functionally tetravalent, binding two antigens on each arm of the IgG molecule simultaneously. This offers a new strategy to also create monospecific, tetravalent IgGs that, depending on antigen architecture and mode-of-action, may have enhanced efficacy compared to traditional bivalent antibodies.


  • Anne Ljungars
  • Torbjörn Schiött
  • Ulrika Mattson
  • Jessica Steppa
  • Björn Hambe
  • Monika Semmrich
  • Mats Ohlin
  • Ulla Carin Tornberg
  • Mikael Mattsson
Enheter & grupper
Externa organisationer
  • Tetra Pak AB
  • BioInvent International AB
  • SenzaGen AB
  • Hansa Medical AB

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
TidskriftScientific Reports
Utgåva nummer1
StatusPublished - 2020 jan 31
Peer review utfördJa