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Engineering antibodies for stability and efficient folding


Honegger, A (2008). Engineering antibodies for stability and efficient folding. In: Chernajovsky, Y; Nissim, A. Therapeutic Antibodies. Berlin, Heidelberg: Springer, 47-68.

Abstract

Antibody variable domains vary widely in their intrinsic thermodynamic stability. Despite the mutual stabilization of the domains in the scFv fragment, most scFv derived from monoclonal antibodies without further engineering show poor to moderate stability. The situation gets more complex for Fab fragments and full-sized antibodies: while the disulfide-linked C(L)/C(H) heterodimer shows very limited thermodynamic stability, its unfolding kinetics are very slow. The same is true for Fab fragments, which, due to this kinetic stabilization, appear to be more stable than their thermodynamic stability suggests. However, suboptimal variable domains can be engineered for improved stability and folding efficiency while preserving their antigen-binding specificity and affinity, either by a limited number of point mutations or by grafting their antigen specificity to superior variable domain frameworks.

Antibody variable domains vary widely in their intrinsic thermodynamic stability. Despite the mutual stabilization of the domains in the scFv fragment, most scFv derived from monoclonal antibodies without further engineering show poor to moderate stability. The situation gets more complex for Fab fragments and full-sized antibodies: while the disulfide-linked C(L)/C(H) heterodimer shows very limited thermodynamic stability, its unfolding kinetics are very slow. The same is true for Fab fragments, which, due to this kinetic stabilization, appear to be more stable than their thermodynamic stability suggests. However, suboptimal variable domains can be engineered for improved stability and folding efficiency while preserving their antigen-binding specificity and affinity, either by a limited number of point mutations or by grafting their antigen specificity to superior variable domain frameworks.

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Additional indexing

Item Type:Book Section, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2008
Deposited On:29 Oct 2008 14:19
Last Modified:14 Sep 2016 13:36
Publisher:Springer
Series Name:Handbook of Experimental Pharmacology
Number:181
ISSN:0171-2004
ISBN:978-3-540-73258-7
Additional Information:978-3-540-73259-4
Publisher DOI:10.1007/978-3-540-73259-4
Official URL:http://www.springerlink.com/content/p7p0u4/
Related URLs:http://www.recherche-portal.ch/primo_library/libweb/action/search.do?fn=search&mode=Advanced&vid=ZAD&vl%28186672378UI0%29=isbn&vl%281UI0%29=contains&vl%28freeText0%29=978-3-540-73258-7
PubMed ID:18071941
Permanent URL: http://doi.org/10.5167/uzh-4815

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