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MAbs. 2013 May-Jun;5(3):358-63. doi: 10.4161/mabs.23977. Epub 2013 Apr 2.

Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule.

Author information

1
Department of Structural Biology; AbbVie Inc.; North Chicago, IL USA.
2
Global Protein Sciences; AbbVie Inc.; North Chicago, IL USA.
3
Cancer Research; AbbVie Inc.; North Chicago, IL USA.
4
Global Biologics; AbbVie BioResearch Center; Worcester, MA USA.

Abstract

Several bispecific antibody-based formats have been developed over the past 25 years in an effort to produce a new generation of immunotherapeutics that target two or more disease mechanisms simultaneously. One such format, the dual-variable domain immunoglobulin (DVD-Ig™), combines the target binding domains of two monoclonal antibodies via flexible naturally occurring linkers, which yields a tetravalent IgG - like molecule. We report the structure of an interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment with IL18 bound to the inner variable domain (VD) that reveals the remarkable flexibility of the DVD-Ig™ molecule and how the DVD-Ig™ format can function to bind four antigens simultaneously. An understanding of how the inner variable domain retains function is of critical importance for designing DVD-Ig™ molecules, and for better understanding of the flexibility of immunoglobulin variable domains and linkers, which may aid in the design of improved bi- and multi-specific biologics in general.

KEYWORDS:

DFab; DVD-Ig™; Dual Specific Antibody; IL12; IL18

PMID:
23549062
PMCID:
PMC4169029
DOI:
10.4161/mabs.23977
[Indexed for MEDLINE]
Free PMC Article

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