Abstract
The dual variable domain immunoglobulin (DVD-IgTM) protein is a new type of dual-specific IgG. As a novel therapeutic class, the great potential of the DVD-Ig protein is to simultaneously target two mediators of disease by a single pharmaceutical entity. The molecule contains an Fc region and constant regions in a configuration similar to a conventional IgG; however, the DVD-Ig protein is unique in that each arm of the molecule contains two variable domains (VDs). The VDs within an arm are linked in tandem and can possess different binding specificities. Here, we discuss critical design features of the DVD-Ig protein and describe a methodology for cloning, expressing, and purifying the molecules.
Key words
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Nelson AL, Dhimolea E, Reichert JM (2010) Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov 9:767–774
Enever C, Batuwangala T, Plummer C, Sepp A (2009) Next generation immunotherapeutics - honing the magic bullet. Curr Opin Biotechnol 20:405–411
Uno T, Takeda K, Kojima Y, Yoshizawa H, Akiba H, Mittler RS et al (2006) Eradication of established tumors in mice by a combination antibody-based therapy. Nat Med 12:693–698
Wu C, Ying H, Grinnell C, Bryant S, Miller R, Clabbers A et al (2007) Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat Biotechnol 25:1290–1297
Wu C, Ying H, Bose S, Miller R, Medina L, Santora L, Ghayur T (2009) Molecular construction and optimization of anti-human IL-1alpha/beta dual variable domain immunoglobulin (DVD-Ig) molecules. MAbs 1(4):339–347
Wu C, Ghayur T, Salfeld J (2010) Generation and characterization of a dual variable domain immunoglobulin (DVD-Ig™) molecule, antibody engineering, vol 2, Chap 19, Roland Kontermann and Stefan Dübel, pp 239–250
Sandin S, Ofverstedt LG, Wikström AC, Wrange O, Skoglund U (2004) Structure and flexibility of individual immunoglobulin G molecules in solution. Structure 12:409–415
Robinson CR, Sauer RT (1998) Optimizing the stability of single-chain proteins by linker length and composition mutagenesis. Proc Natl Acad Sci U S A 95:5929–5934
Hsieh C-M (2009) Improved mammalian expression vectors and uses thereof. US PCT/US2009/031136
Sun X, Hia HC, Goh PE et al (2008) High-density transient gene expression in suspension-adapted 293 EBNA1 cells. Biotechnol Bioeng 99:108–116
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
DiGiammarino, E., Ghayur, T., Liu, J. (2012). Design and Generation of DVD-Ig™ Molecules for Dual-Specific Targeting. In: Voynov, V., Caravella, J. (eds) Therapeutic Proteins. Methods in Molecular Biology, vol 899. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-921-1_9
Download citation
DOI: https://doi.org/10.1007/978-1-61779-921-1_9
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61779-920-4
Online ISBN: 978-1-61779-921-1
eBook Packages: Springer Protocols