Training of epitope-TCR prediction models with healthy donor-derived cancer-specific T cells.

Journal: Methods in cell biology
PMID: 38548410

Abstract

Discovery of epitope-specific T-cell receptors (TCRs) for cancer therapies is a time consuming and expensive procedure that usually requires a large amount of patient cells. To maximize information from and minimize the need of precious samples in cancer research, prediction models have been developed to identify in silico epitope-specific TCRs. In this chapter, we provide a step-by-step protocol to train a prediction model using the user-friendly TCRex webtool for the nearly universal tumor-associated antigen Wilms' tumor 1 (WT1)-specific TCR repertoire. WT1 is a self-antigen overexpressed in numerous solid and hematological malignancies with a high clinical relevance. Training of computational models starts from a list of known epitope-specific TCRs which is often not available for new cancer epitopes. Therefore, we describe a workflow to assemble a training data set consisting of TCR sequences obtained from WT1-reactive CD8 T cell clones expanded and sorted from healthy donor peripheral blood mononuclear cells.

Authors

  • Donovan Flumens
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
  • Sofie Gielis
    Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium.
  • Esther Bartholomeus
    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), VAXINFECTIO, University of Antwerp, Antwerp, Belgium; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
  • Diana Campillo-Davo
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
  • Sanne van der Heijden
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium.
  • Maarten Versteven
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
  • Hans De Reu
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
  • Evelien Smits
    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), VAXINFECTIO, University of Antwerp, Antwerp, Belgium.
  • Benson Ogunjimi
    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Centre for Health Economics Research & Modeling Infectious Diseases (CHERMID), VAXINFECTIO, University of Antwerp, Antwerp, Belgium; Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium.
  • Kris Laukens
    Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium.
  • Pieter Meysman
    Adrem Data Lab, Department of Computer Science, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Biomedical Informatics Research Network Antwerp (Biomina), University of Antwerp, Antwerp, Belgium.
  • Eva Lion
    Laboratory of Experimental Hematology (LEH), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium; Center for Cell Therapy & Regenerative Medicine (CCRG), Antwerp University Hospital, Edegem, Belgium. Electronic address: eva.lion@uantwerpen.be.

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