Fenn, Sebastian; Schiller, Christian B.; Griese, Julia J.; Duerr, Harald; Imhof-Jung, Sabine; Gassner, Christian; Moelleken, Joerg; Regula, Joerg Thomas; Schaefer, Wolfgang; Thomas, Markus; Klein, Christian; Hopfner, Karl-Peter; Kettenberger, Hubert
(2013):
Crystal Structure of an Anti-Ang2 CrossFab Demonstrates Complete Structural and Functional Integrity of the Variable Domain.
In: PLOS ONE
8(4), e61953
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Abstract
Bispecific antibodies are considered as a promising class of future biotherapeutic molecules. They comprise binding specificities for two different antigens, which may provide additive or synergistic modes of action. There is a wide variety of design alternatives for such bispecific antibodies, including the "CrossMab" format. CrossMabs contain a domain crossover in one of the antigen-binding (Fab) parts, together with the "knobs-and-holes" approach, to enforce the correct assembly of four different polypeptide chains into an IgG-like bispecific antibody. We determined the crystal structure of a hAng-2-binding Fab in its crossed and uncrossed form and show that CH1-CL-domain crossover does not induce significant perturbations of the structure and has no detectable influence on target binding.