Research Project
NeoHLA-Map – A Versatile Immunopeptidomics Platform for Functional Identification of (Neo-)Epitopes
Various approaches have been developed for the direct identification of human leukocyte antigen (HLA)-presented peptides using high-sensitivity mass spectrometry (immunopeptidomics) on transformed cells. The main aim of such methods is discovering actionable targets for therapeutic cancer vaccines or adoptive T cell therapies. However, in everyday clinical practice, sample material is often limited and hampers the broad application of immunopeptidomics. While in silico binding prediction is often used to select potential target epitopes, these are not necessarily presented by tumor cells.
The first goal of this project is to establish a platform for the identification of naturally processed and presented (neo-)epitopes by mass spectrometry from the respective cancer immunopeptidome. Mono-allelic HLA class I cell lines will be generated from different cancer-derived cell lines, starting with HPV-associated cervical cancer cell lines already established in the lab. In combination with tandem minigenes encoding viral and mutation-derived neoepitopes or tumor-associated antigens, this modular toolbox will allow the investigation of epitope presentation with broad population coverage in diverse cancer backgrounds. Using established cell lines for which extensive datasets are already available in the group allows for benchmarking of the platform to ensure minimal deviation of the immunopeptidome compared to the unmodified cell lines.
Using the established platform, differences in peptide presentation between HLA subtypes will be elucidated by generating epitome maps for combinations of common HLA alleles and frequent tumor-specific and/or tumor-associated antigens. To test the different HLA:epitope combinations for T cell recognition, the established cell lines will be integrated into an existing live cell microscopy-based cytotoxicity assay. Moreover, the platform will be used to generate “patient surrogates” in order to investigate the potential presentability of mutation-derived neoepitopes even in the absence of actual patient tumor material.
To expand the current immunopeptidomics method repertoire of the group, it is planned to implement a hybrid PRM/DIA approach, which will allow targeting previously identified (neo-)epitope panels in patient tumor samples with ultra-high sensitivity while also generating a digital map of the sample which can be searched for patient-specific (neo-)epitopes from the same measurement.
Overall, the project will provide a valuable tool to identify actionable (neo-)epitopes and investigate their benefit for treating large patient cohorts using both personalized and so-called warehouse approaches.
Scientific CV
Since Oct 2025
PhD student, Immunotherapy and Immunoprevention, DKFZ, Heidelberg
2023 - 2025
MSc Biotechnology (with Major in Biomedical Science and Technology), Technische Hochschule Mannheim, Cellzome – A GSK Company
2019 – 2023
BSc Biotechnology, Technische Hochschule Mannheim, Cellzome – A GSK Company (including a research stay at Memorial University of Newfoundland, Canada)