Mogjiborahman Salek

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Mass spectrometry-based identification of mutation-derived tumor neoepitopes

To differentiate tumor cells from normal cells, the immune system needs to recognize structures that are tumor-specific. Altered proteins resulting from tumor-specific mutations – so-called neoantigens - fulfil this requirement, and are thus attractive targets for immunotherapy approaches. However, it is not yet clear which epitopes derived from neoantigens (i.e. "neoepitopes") are actually presented to the immune system on the tumor cell surface, as they mostly are of low abundance and therefore difficult to detect. But only presented neoepitopes represent meaningful targets for epitope-specific vaccines or adoptive transfer of T cells with transgenic T cell receptors.
A targeted mass spectrometry (MS) approach has been developed in the lab to detect low abundance epitopes. It has successfully been applied to detect neoepitopes. This research project aimed at establishing a high-throughput neoepitope detection workflow using the most recent mass spectrometry technology and advanced bioinformatics. The developed workflow is applicable for every tumor for which the tumor-specific mutations have been identified by genome sequencing, and for which samples are available for MS analysis. The analysis provides a rational basis for the development of immunotherapies by providing validated target neoepitopes.