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Fc Engineering: Tailored Synthetic Human IgG1-Fc Repertoire for High-Affinity Interaction with FcRn at pH 6.0

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Antibody Engineering

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1827))

Abstract

The therapeutic efficacy of an antibody drug depends on the variable domains and on the constant crystallizable fragment (Fc). IgG variable domains have been the targets of extensive molecular engineering in search of more specific binders with higher affinities for their targets. Similarly, Fc engineering approaches have led to modulating both the immune effector responses and serum half-lives of therapeutic antibodies. A high-affinity interaction between the IgG Fc and neonatal Fc receptor (FcRn) at a slightly acidic pH can protect IgG molecules from undergoing lysosomal or serum proteinase-induced degradation. Here we describe an optimized protocol for the development of a tailored, synthetic human Fc repertoire to select Fc mutants which show highly pH-restricted FcRn binding with high affinity.

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (Grant No.: 81572698 and 31771006) to DW.

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Authors and Affiliations

  1. Laboratory of Antibody Engineering, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China

    Abhishek Saxena, Bingxin Bai, Shin-Chen Hou, Lianlian Jiang, Sachdev S. Sidhu & Donghui Wu

  2. Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, Shanghai, China

    Tianlei Ying

  3. Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada

    Shane Miersch & Sachdev S. Sidhu

  4. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Sachdev S. Sidhu

Authors
  1. Abhishek Saxena
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  2. Bingxin Bai
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  3. Shin-Chen Hou
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  4. Lianlian Jiang
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  5. Tianlei Ying
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  6. Shane Miersch
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  7. Sachdev S. Sidhu
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  8. Donghui Wu
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Corresponding authors

Correspondence to Sachdev S. Sidhu or Donghui Wu .

Editor information

Editors and Affiliations

  1. Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

    Damien Nevoltris

  2. Institut Paoli-Calmettes, CRCM, Aix Marseille University, CNRS, INSERM, Marseille, France

    Patrick Chames

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Saxena, A. et al. (2018). Fc Engineering: Tailored Synthetic Human IgG1-Fc Repertoire for High-Affinity Interaction with FcRn at pH 6.0. In: Nevoltris, D., Chames, P. (eds) Antibody Engineering. Methods in Molecular Biology, vol 1827. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8648-4_21

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  • DOI: https://doi.org/10.1007/978-1-4939-8648-4_21

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8647-7

  • Online ISBN: 978-1-4939-8648-4

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