Expitope: a web server for epitope expression

Kerstin Haase1, Silke Raffegerst2, Dolores J Schendel2

  • 1Department of Genome Oriented Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität München, 85354 Freising, Germany, Immune Monitoring Group, Helmholtz Zentrum Munich, Institute of Molecular Immunology, 81377 München, Germany, Medigene Immunotherapies GmbH a Subsidiary of Medigene AG, 82152 Planegg, Germany, Helmholtz Zentrum Munich, Institute of Bioinformatics and Systems Biology, 85764 Neuherberg, Germany and St Petersburg State Polytechnical University, St Petersburg, 195251, Russia.

Abstract

Insights

Designing adoptive T cell therapies requires careful antigen selection to avoid self-antigen reactivity. The Expitope web server identifies potential epitope sharing in target antigens, aiding in the early selection of safe T cell receptors (TCRs).

Area of Science:

  • Immunology
  • Bioinformatics
  • Cancer Therapy

Background:

  • Adoptive T cell therapies using engineered T cell receptors (TCRs) show promise for cancer treatment.
  • A critical challenge is selecting target antigens to prevent devastating side-effects from self-antigen cross-reactivity.

Purpose of the Study:

  • To present the first web server, Expitope, for assessing epitope sharing in potential cancer immunotherapy targets.
  • To provide a tool for early-stage exclusion of cross-reactive antigens during TCR design.

Main Methods:

  • The Expitope web server identifies exact and approximate matches for user-provided peptides within known proteins.
  • It analyzes RNA sequencing data to assess protein expression in healthy and cancer tissues.
  • Results are scored based on predicted proteasomal cleavage, transporter associated with antigen processing (TAP) affinity, and MHC class I allele binding.

Main Results:

  • The server finds all known proteins containing a user's peptide of interest, including near matches.
  • Expression levels in various human tissues and cancer types are provided.
  • Results are ranked by a comprehensive immunological prediction score.

Conclusions:

  • Expitope serves as a valuable tool for researchers designing adoptive T cell immunotherapies.
  • It facilitates the exclusion of potentially cross-reactive epitopes early in the TCR selection process.
  • This aids in developing safer and more effective cancer treatments.