Engineered Autonomous Human Variable Domains

Author(s): Johan Nilvebrant , Peter M. Tessier , Sachdev S. Sidhu .

Journal Name: Current Pharmaceutical Design

Volume 22 , Issue 43 , 2016

Abstract:

Background: The complex multi-chain architecture of antibodies has spurred interest in smaller derivatives that retain specificity but can be more easily produced in bacteria. Domain antibodies consisting of single variable domains are the smallest antibody fragments and have been shown to possess enhanced ability to target epitopes that are difficult to access using multidomain antibodies. However, in contrast to natural camelid antibody domains, human variable domains typically suffer from low stability and high propensity to aggregate.

Methods: This review summarizes strategies to improve the biophysical properties of heavy chain variable domains from human antibodies with an emphasis on aggregation resistance. Several protein engineering approaches have targeted antibody frameworks and complementarity determining regions to stabilize the native state and prevent aggregation of the denatured state.

Conclusion: Recent findings enable the construction of highly diverse libraries enriched in aggregation-resistant variants that are expected to provide binders to diverse antigens. Engineered domain antibodies possess unique advantages in expression, epitope preference and flexibility of formatting over conventional immunoreagents and are a promising class of antibody fragments for biomedical development.

Keywords: Human domain antibody, variable heavy domain, antibody engineering, synthetic antibodies, phage display, aggregation.

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Article Details

VOLUME: 22
ISSUE: 43
Year: 2016
Page: [6527 - 6537]
Pages: 11
DOI: 10.2174/1381612822666160921143011
Price: $58

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