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PITHA: A Webtool to Predict Immunogenicity for Humanized and Fully Human Therapeutic Antibodies

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Computer-Aided Antibody Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2552))

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Abstract

Immunogenicity is an important concern to therapeutic antibodies during antibody design and development. Based on the co-crystal structures of idiotypic antibodies and their antibodies, one can see that anti-idiotypic antibodies usually bind the complementarity-determining regions (CDR) of idiotypic antibodies. Sequence and structural features, such as cavity volume at the CDR region and hydrophobicity of CDR-H3 loop region, were identified for distinguishing immunogenic antibodies from non-immunogenic antibodies. These features were integrated together with a machine learning platform to predict immunogenicity for humanized and fully human therapeutic antibodies (PITHA). This method achieved an accuracy of 83% in a leave-one-out experiment for 29 therapeutic antibodies with available crystal structures. The web server of this method is accessible at http://mabmedicine.com/PITHA or http://sysbio.unl.edu/PITHA. This method, as a step of computer-aided antibody design, helps evaluate the safety of new therapeutic antibody, which can save time and money during the therapeutic antibody development.

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Acknowledgments

This work was completed utilizing the Holland Computing Center of the University of Nebraska. Bio-Thera Solutions owns the patent right relating to the algorithm described in this chapter.

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Authors and Affiliations

  1. Department of Research and Development, Bio-Thera Solutions, Guangzhou, P. R. China

    Shide Liang

  2. School of Biological Sciences, University of Nebraska, Lincoln, NE, USA

    Chi Zhang

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  1. Shide Liang
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  2. Chi Zhang
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Correspondence to Chi Zhang .

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Editors and Affiliations

  1. School of Engineering, The University of Tokyo, Tokyo, Japan

    Kouhei Tsumoto

  2. School of Engineering, The University of Tokyo, Tokyo, Japan

    Daisuke Kuroda

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Liang, S., Zhang, C. (2023). PITHA: A Webtool to Predict Immunogenicity for Humanized and Fully Human Therapeutic Antibodies. In: Tsumoto, K., Kuroda, D. (eds) Computer-Aided Antibody Design. Methods in Molecular Biology, vol 2552. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2609-2_7

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  • DOI: https://doi.org/10.1007/978-1-0716-2609-2_7

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2608-5

  • Online ISBN: 978-1-0716-2609-2

  • eBook Packages: Springer Protocols

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