Skip Navigation



PEDS Advance Access published online on November 3, 2007
Protein Engineering Design and Selection, doi:10.1093/protein/gzm061
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
20/11/569    most recent
gzm061v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Stork, R.
Right arrow Articles by Kontermann, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stork, R.
Right arrow Articles by Kontermann, R. E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

A novel tri-functional antibody fusion protein with improved pharmacokinetic properties generated by fusing a bispecific single-chain diabody with an albumin-binding domain from streptococcal protein G

Roland Stork, Dafne Müller and Roland E. Kontermann1

Institut für Zellbiologie und Immunologie, Universität Stuttgart, Allmandring 31, 70569 Stuttgart, Germany

1 To whom correspondence should be addressed. E-mail: roland.kontermann{at}izi.uni-stuttgart.de

The therapeutic application of small recombinant antibody molecules is often limited by a short serum half-life. In order to improve the pharmacokinetic properties, we have investigated a strategy utilizing fusion with an albumin-binding domain (ABD) from streptococcal protein G. This strategy was applied to a bispecific single-chain diabody (scDb CEACD3) developed for the retargeting of cytotoxic T cells to CEA-expressing tumor cells. This novel tri-functional fusion protein (scDb–ABD) was expressed in mammalian cells and recognized both antigens as well as human and mouse serum albumin. scDb–ABD was capable to retarget T cells to CEA-expressing target cells in vitro and to activate the effector cells as measured by stimulation of IL-2 release. Although activity was reduced 3-fold compared with scDb and further reduced 4-fold in the presences of human serum albumin, this assay demonstrated that scDb–ABD is active when exposed to all three antigens. Compared with scDb, the circulation time of scDb–ABD in mice was prolonged 5- to 6-fold similar to a previously described scDb–HSA fusion protein. This strategy, which adds only a small protein domain (46 amino acids) and which utilizes high-affinity, non-covalent albumin interaction, should be broadly applicable to improve serum half-lives of small recombinant antibody molecules.

Keywords: albumin-binding domain/bispecific antibody/effector cells/pharmacokinetics/tri-functional antibody

Received July 12, 2007; revised September 28, 2007; accepted October 2, 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Protein Eng Des SelHome page
A. Jonsson, J. Dogan, N. Herne, L. Abrahmsen, and P.-A. Nygren
Engineering of a femtomolar affinity binding protein to human serum albumin
Protein Eng. Des. Sel., August 1, 2008; 21(8): 515 - 527.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.