4hjj

Publication Abstract from PubMed

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.

Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig) molecule.,Jakob CG, Edalji R, Judge RA, Digiammarino E, Li Y, Gu J, Ghayur T MAbs. 2013 Apr 2;5(3). PMID:23549062^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.