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

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 Expito...

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Autores principales: Jaravine, Victor, Mösch, Anja, Raffegerst, Silke, Schendel, Dolores J., Frishman, Dmitrij
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745885/
https://www.ncbi.nlm.nih.gov/pubmed/29282079
http://dx.doi.org/10.1186/s12885-017-3854-8
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author Jaravine, Victor
Mösch, Anja
Raffegerst, Silke
Schendel, Dolores J.
Frishman, Dmitrij
author_facet Jaravine, Victor
Mösch, Anja
Raffegerst, Silke
Schendel, Dolores J.
Frishman, Dmitrij
author_sort Jaravine, Victor
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3854-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-57458852018-01-03 Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues Jaravine, Victor Mösch, Anja Raffegerst, Silke Schendel, Dolores J. Frishman, Dmitrij BMC Cancer Software 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3854-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-28 /pmc/articles/PMC5745885/ /pubmed/29282079 http://dx.doi.org/10.1186/s12885-017-3854-8 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Software
Jaravine, Victor
Mösch, Anja
Raffegerst, Silke
Schendel, Dolores J.
Frishman, Dmitrij
Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title_full Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title_fullStr Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title_full_unstemmed Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title_short Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
title_sort expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues
topic Software
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745885/
https://www.ncbi.nlm.nih.gov/pubmed/29282079
http://dx.doi.org/10.1186/s12885-017-3854-8
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