Biophysical and biochemical characterization of a VHH-based IgG-like bi- and trispecific antibody platform. Issue 1 (1st January 2020)

• Record Type: Journal Article
• Authors: Pekar, Lukas; Busch, Michael; Valldorf, Bernhard; Hinz, Steffen C.; Toleikis, Lars; Krah, Simon; Zielonka, Stefan
• Is Part Of: MAbs. Volume 12:Issue 1(2020)
• Publication Date: 2020-01-01
• Subjects: Antibody engineering -- bispecific antibody -- camelid -- IgG-like -- nanobody -- single-domain antibody -- trispecific antibody -- VHH; Monoclonal antibodies -- Therapeutic use -- Periodicals; Monoclonal antibodies -- Periodicals; Antibodies, Monoclonal -- Periodicals; 616.0798
• DOI: 10.1080/19420862.2020.1812210
• Languages: English
• ISSNs: 1942-0862

Abstract

ABSTRACT: Here, we report the characterization of a VHH-derived IgG-like bi- and trispecific antibody platform that essentially relies on the replacement of the VH and VL regions of a conventional antibody by two independently functioning VHH domains. Consequently, a VHH is engrafted onto constant region CH1 while the other VHH-based paratope is engrafted on the constant region of the light chain, Cκ or Cλ, resulting in a tetravalent bispecific IgG-like molecule. Combined with a heavy chain heterodimerization technique, this platform allows facile engineering of bi- and trispecific antibodies with flexible valencies. We demonstrate the general applicability of this generic platform approach and elaborate on the limitations of specific formats.