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Comment
. 2017 Sep 1;292(35):14718-14719.
doi: 10.1074/jbc.H117.793497.

Opposites attract in bispecific antibody engineering

Marit J van Gils  1 , Rogier W Sanders  2   3
Affiliations
Comment

Opposites attract in bispecific antibody engineering

Marit J van Gils et al. J Biol Chem. .

Abstract

Bispecific antibodies show great promise as intrinsic combination therapies, but often suffer from poor physiochemical properties, many times related to poor heterodimerization. De Nardis et al. identify specific electrostatic interactions that facilitate efficient heterodimerization, resulting in bispecific antibodies with physiochemical properties very similar to those of naturally occurring antibodies. This provides a new platform for the treatment of an array of diseases from cancer and autoimmune diseases to infectious diseases.

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Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article.

Figures

Figure 1.
Figure 1.
Engineering of a DEKK bispecific antibody. A cartoon of a heterodimeric antibody with the different domains of the heavy and light chain labeled is shown on the left. The middle panel shows the protein structure of the DEKK CH3 domains (PDB entry 5NSC), while the right panel reveals the molecular interactions of the DEKK substitutions (Asp-351, Glu-368, Lys-351, Lys-366) in which the individual substitutions are highlighted; interacting residues are indicated in similar colors. Fab, antigen-binding fragment; Fc, crystallizable fragment; VL, light-chain variable region; CL, light-chain constant region; VH, heavy-chain variable region; CH1–3, heavy-chain constant regions 1–3.
See this image and copyright information in PMC

Comment on

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