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Biophysical and biochemical characterization of a VHH-based IgG-like bi- and trispecific antibody platform.

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.

SUBMITTER: Pekar L

PROVIDER: S-EPMC7531565 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Biophysical and biochemical characterization of a VHH-based IgG-like bi- and trispecific antibody platform.

Pekar Lukas L Busch Michael M Valldorf Bernhard B Hinz Steffen C SC Toleikis Lars L Krah Simon S Zielonka Stefan S

mAbs 20200101 1

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 heterodimeriza ...[more]

PMID: 32887531

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