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. 2017 Dec 28;17(1):892.
doi: 10.1186/s12885-017-3854-8.

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

Victor Jaravine  1   2 , Anja Mösch  1   2 , Silke Raffegerst  2 , Dolores J Schendel  2 , Dmitrij Frishman  3   4
Affiliations

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

Victor Jaravine et al. BMC Cancer. .

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.

Keywords: Cancer; Cross-reactivity; Immunoinformatics; Immunotherapy; T cell epitope; Tumor antigen expression; Tumor immunology.

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Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

VJ, AM and SR are employees of Medigene Immunotherapies GmbH/Medigene AG. DJS is Managing Director of Medigene Immunotherapies GmbH and CEO/CSO of Medigene AG.

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Figures

Fig. 1
Fig. 1
Workflow of the Expitope 2.0 web server
Fig. 2
Fig. 2
The I CR indices for the four IEDB peptide groups (Table 2), obtained by averaging over the seven databases listed in Table 1. Q=2e-2 (left), Q=1e-4 (right), with up to one mismatch (K=1). Thick black line: median; gray: the lower and the upper quartiles (25th and 75th percentiles); upper and lower whiskers: highest and lowest values
See this image and copyright information in PMC

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