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Transgenic Animals for the Generation of Human Antibodies

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Introduction to Antibody Engineering

Part of the book series: Learning Materials in Biosciences ((LMB))

What You Will Learn in This Chapter

Currently, 28% of all monoclonal antibody (mAb) therapies and 74% of fully human mAb therapies approved by US Food and Drug Administration (FDA) are derived from transgenic animal platforms. In these platforms, the host antibody heavy chain VDJ and light chain VJ repertoire are substituted by their counterparts which are encoded exclusively by human transgenes. These platforms take advantage of the host’s naturally antigen-driven antibody selection and maturation process associated with the primary and secondary immune response. Through immunisations and subsequent antibody discovery using common technologies including hybridoma and single B-cell screening, a large panel of mAbs exhibiting high affinity and specificity against the target antigen along with ideal biophysical characteristics and developability can be obtained. They can be streamlined into clinical development. This chapter gives a comprehensive overview of the transgenic strategies, methods of creating knockout of the endogenous immunoglobulin (Ig) production and generation of transgenic constructs containing human Ig heavy and light chain gene locus. Brief introductions are also given to a list of representative transgenic platforms which have originated in multiple species and can produce human antibodies in various formats. The strategies for antibody discovery in these platforms are also discussed.

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Author information

Authors and Affiliations

  1. Apollomics Inc, Xiaoshan, Hangzhou, China

    Biao Ma

  2. Teniobio, Newark, CA, USA

    Michael Osborn

  3. LifeArc, SBC Open Innovation Campus, Stevenage, UK

    Michael Osborn

Authors
  1. Biao Ma
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  2. Michael Osborn
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Editor information

Editors and Affiliations

  1. Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU), Vienna, Austria

    Florian Rüker

  2. Christian Doppler Laboratory for Innovative Immunotherapeutics, Institute of Molecular Biotechnology, Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna (BOKU), Vienna, Austria

    Gordana Wozniak-Knopp

Further Reading

Further Reading

  • Almagro JC, Daniels-Wells TR, Perez-Tapia SM, Penichet ML. Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy. Front Immunol 2018; 8:1751

  • Brüggemann M, Osborn MJ, Ma B, Buelow R. Strategies to obtain diverse and specific Human monoclonal antibodies from transgenic animals. Transplantation 2017; 101(8):1770–1776

  • Chen WC, Murawsky CM. Strategies for Generating Diverse Antibody Repertoires Using Transgenic Animals Expressing Human Antibodies. Front Immunol 2018; 9:460.

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Ma, B., Osborn, M. (2021). Transgenic Animals for the Generation of Human Antibodies. In: Rüker, F., Wozniak-Knopp, G. (eds) Introduction to Antibody Engineering. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-54630-4_5

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