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Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Software

Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues

Authors: Victor Jaravine, Anja Mösch, Silke Raffegerst, Dolores J. Schendel, Dmitrij Frishman

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Adoptive immunotherapy offers great potential for treating many types of cancer but its clinical application is hampered by cross-reactive T cell responses in healthy human tissues, representing serious safety risks for patients. We previously developed a computational tool called Expitope for assessing cross-reactivity (CR) of antigens based on tissue-specific gene expression. However, transcript abundance only indirectly indicates protein expression. The recent availability of proteome-wide human protein abundance information now facilitates a more direct approach for CR prediction. Here we present a new version 2.0 of Expitope, which computes all naturally possible epitopes of a peptide sequence and the corresponding CR indices using both protein and transcript abundance levels weighted by a proposed hierarchy of importance of various human tissues.

Results

We tested the tool in two case studies: The first study quantitatively assessed the potential CR of the epitopes used for cancer immunotherapy. The second study evaluated HLA-A*02:01-restricted epitopes obtained from the Immune Epitope Database for different disease groups and demonstrated for the first time that there is a high variation in the background CR depending on the disease state of the host: compared to a healthy individual the CR index is on average two-fold higher for the autoimmune state, and five-fold higher for the cancer state.

Conclusions

The ability to predict potential side effects in normal tissues helps in the development and selection of safer antigens, enabling more successful immunotherapy of cancer and other diseases.
Appendix
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Metadata
Title
Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
Authors
Victor Jaravine
Anja Mösch
Silke Raffegerst
Dolores J. Schendel
Dmitrij Frishman
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3854-8

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