Expitope 2.0 helps to identify safer antigens for immunotherapy of cancer

Planegg - - Published article in "BMC Cancer" shows how to predict potential side effects in normal tissues
- Medigene will continue to add further functionalities to in-house version of Expitope 2.0

Martinsried/Munich, 4 January 2018. Medigene AG (MDG1, Frankfurt, Prime Standard, TecDAX) announces that a scientific article has been published in the current issue of "BMC Cancer". This article describes Expitope 2.0, a tool for the assessment of immunotherapeutic antigens on their similarity to naturally expressed proteins in human tissues. This similarity can lead to cross-reactivity triggered by T cells utilized in immunotherapeutic treatments.

The authors of the paper have added new functionalities to Expitope, a previously described computational tool. Expitope was developed by Technical University of Munich and Medigene for assessing cross-reactivity (CR) of antigens based on tissue-specific patterns of gene expression. However, transcript abundance, although highly correlated, only indirectly indicates protein expression levels in cells. The now available information about protein abundance in the human body facilitates a more direct approach for CR prediction.

In the published research article, a new version 2.0 of Expitope is presented, which computes CR indices using both protein and transcript abundance levels and weights them by a proposed hierarchy of importance of various human tissues. The algorithm predicts all naturally possible self-antigens for a given sequence of a therapeutic antigen (or epitope), and ranks these by potential immunogenicity. Medigene has added additional functionalities to the new version and will continue to further develop the tool in-house for faster and more precise target antigen predictions.

Prof. Dr. Dolores J. Schendel, CEO and CSO of Medigene AG, comments: "The newly described and tested version of Expitope 2.0 is the basis for additional functional expansions that Medigene now runs on its in-house IT infrastructure. It enables us and our partners to select the best possible antigen candidates for more successful immunotherapy of cancer and other diseases by predicting potential side effects in normal tissues."

The tool was tested in two case studies: The first one included all MHC-class-I epitopes provided by the cancer immunity peptide database (n=347) and quantitatively assessed the potential CR of the epitopes used for cancer immunotherapy. The second case study included all HLA-A*02:01-restricted epitopes (n=1720) from selected disease groups, obtained from the Immune Epitope Database. For the first time, the authors could demonstrate that different disease groups show a high variation in the background CR depending on the disease state of the host. Compared to a healthy individual the CR index is of these are on average two-fold higher for the autoimmune state, and five-fold higher for the cancer state.

The article entitled "Expitope 2.0: a tool to assess immunotherapeutic antigens for their potential cross-reactivity against naturally expressed proteins in human tissues" can be found here online: doi.org/10.1186/s12885-017-3854-8

The results have been generated by scientists from the Department of Bioinformatics of TUM School of Life Sciences Weihenstephan, Technical University of Munich, Medigene Immunotherapies GmbH, a subsidiary of Medigene AG, and the St Petersburg State Polytechnical University, Russia.

About Medigene's TCR technology: The TCR technology aims at arming the patient's own T cells with tumor-specific T-cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient's tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient's T cells outside the body (ex vivo).
Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, TecDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies, with associated projects currently in pre-clinical and clinical development.
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