Hi-TIDe : Immunopeptidomics

Our main goal is to identify clinically relevant cancer specific Human Leukocyte Antigen (HLA) ligands that will guide the development of personalized cancer immunotherapy using mass-spectrometry (MS), currently the only methodology to unbiasedly identify HLA binding peptides that are presented in vivo to cytotoxic T cells.

MS-based immunopeptidomics with proteomics, genomics, and transcriptomics to identify tumor-associated antigens, neoantigens and post translationally modified peptides.

We developed a high-throughput and in depth MS-based immunopeptidomics pipeline that now enables robust and reproducible sample preparation and measurement of HLA class I and HLA class II peptides. We are currently applying this methodology to identify tumor-associated HLA ligands extracted from cell lines and tumor tissues. 

• We have initiated fundamental discovery work to elucidate how tumor cells present antigens and what are the bases of tumor immunogenicity.
• We are investigating the differences between tumor types in terms of antigen presentation and how drugs modulate the immunopeptidome.
• In collaboration with the Vital-IT group (SIB), we have established a continuous bio-informatics pipline enabling direct identification of neoantigens by combining genomic information derived from exome-seq analysis with measured immunopeptidomics data.
• In collaboration with Prof. David Gfeller, we are improving the performance of HLA binding prediction tools by training them with our measured immunopeptidomics data.
• This platform will be used to identify personalized neo-antigens from patients samples collected by the CTE team. These tumor-specific antigens will be further developed into personalized cancer vaccines or to enrich tumor-reactive and antigen-specific T cells for adoptive T cell-based therapies.

• Müller M, Gfeller D, Coukos G and Bassani-Sternberg M* (2017) *Corresponding author. Hotspots of Antigen Presentation Revealed by HLA Ligandomics For Neoantigen Prioritization. Frontiers in Immunology, in press.

• *Bassani-Sternberg, M., C. Chong, P. Guillaume, M. Solleder, H. Pak, P. O. Gannon, L. E. Kandalaft, G. Coukos and *D. Gfeller. Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity. PLoS Comput Biol 13(8): e1005725 (2017) *Corresponding authors

• *Caron, E., R. Aebersold, A. Banaei-Esfahani, C. Chong and *M. Bassani-Sternberg (2017). A Case for a Human Immuno-Peptidome Project Consortium. Immunity 47(2): 203-208 (2017). *Corresponding authors
   
• *Bassani-Sternberg, M., *E. Braunlein, R. Klar, T. Engleitner, P. Sinitcyn, S. Audehm, M. Straub, J. Weber, J. Slotta-Huspenina, K. Specht, M. E. Martignoni, A. Werner, R. Hein, H. B. D, C. Peschel, R. Rad, J. Cox, M. Mann and A. M. Krackhardt . Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat Commun 7: 13404 (2016)
   
• Bassani-Sternberg, M. and G. Coukos. Mass spectrometry-based antigen discovery for cancer immunotherapy.Curr Opin Immunol 41: 9-17 (2016).