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Engineering Antibodies for Stability and Efficient Folding

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Therapeutic Antibodies

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 181))

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 fullsized antibodies: while the disulfide-linked CL/CH 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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Authors and Affiliations

  1. Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    A. Honegger

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  1. A. Honegger
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Editors and Affiliations

  1. ARC Chair of Rheumatology, Centre Lead Bone & Joint Research Unit, Queen Mary's School of Medicine & Dentistry John Vane Science Centre, Charterhouse Square, EC1M 6BQ, London, UK

    Yuti Chernajovsky

  2. Bone & Joint Research Unit, Queen Mary's School of Medicine & Dentistry John Vane Science Centre, Charterhouse Square, EC1M 6BQ, London, UK

    Ahuva Nissim

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Honegger, A. (2008). Engineering Antibodies for Stability and Efficient Folding. In: Chernajovsky, Y., Nissim, A. (eds) Therapeutic Antibodies. Handbook of Experimental Pharmacology, vol 181. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73259-4_3

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