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Related Experiment Videos

Engineering antibodies for stability and efficient folding.

A Honegger1

  • 1Biochemisches Institut, Universität Zürich, Winterthurerstrasse 190, Zürich, Switzerland. honegger@bioc.uzh.ch

Handbook of Experimental Pharmacology
|December 12, 2007
PubMed
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Antibody variable domains exhibit diverse stability. Engineering can improve stability and folding efficiency of antibody fragments like scFv and Fab, preserving antigen binding.

Area of Science:

  • Biochemistry
  • Immunology
  • Protein Engineering

Background:

  • Antibody variable domains display a wide range of intrinsic thermodynamic stability.
  • Single-chain variable fragments (scFv) often show limited stability despite domain mutual stabilization.
  • Fab fragments and full-sized antibodies exhibit slow unfolding kinetics, contributing to apparent stability despite low thermodynamic stability.

Purpose of the Study:

  • To investigate the thermodynamic stability and kinetic stabilization of antibody variable domains.
  • To explore methods for engineering improved stability and folding efficiency in antibody fragments.
  • To ensure preservation of antigen-binding specificity and affinity during stability engineering.

Main Methods:

  • Thermodynamic stability analysis of antibody variable domains.

Related Experiment Videos

  • Kinetic unfolding studies of antibody fragments (scFv, Fab, full-sized antibodies).
  • Engineering strategies including point mutations and domain grafting for stability enhancement.

    • Main Results:

    • Most engineered scFv fragments show poor to moderate stability without specific engineering.
    • Disulfide-linked C(L)/C(H) heterodimers in larger antibody formats have limited thermodynamic stability but slow unfolding kinetics.
    • Fab fragments benefit from kinetic stabilization, appearing more stable than their thermodynamics suggest.
    • Engineering approaches like point mutations and framework grafting can enhance stability and folding efficiency while maintaining antigen specificity and affinity.

    Conclusions:

    • Intrinsic thermodynamic stability varies significantly among antibody variable domains.
    • Kinetic stabilization plays a crucial role in the observed stability of antibody fragments and full-sized antibodies.
    • Antibody variable domains can be successfully engineered for enhanced stability and folding efficiency without compromising antigen-binding properties.