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.

Proteogenomics and MS-based immunopeptidomics approaches to identify HLA ligands derived from tumor-associated proteins, mutated neoantigens, non-canonical ORFs 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/MHC class I and class II peptides. We are currently applying this methodology to identify tumor-associated ligands extracted from cell lines and tumor tissues from humans and nice models. 
• 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 pipeline enabling direct identification of neoantigens by combining genomic information derived from exome-seq analysis with measured immunopeptidomics data.
• In collaboration with Pr David Gfeller, we are improving the performance of HLA class I and class II binding prediction tools by training them with our measured immunopeptidomics data.
• We apply proteogenomics approaches to identify personalized neo-antigens from patient tumor samples. 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.

• Julien Racle, Justine Michaux, Georg Alexander Rockinger, Marion Arnaud, Philippe Guillaume, Sara Bobisse, George Coukos, Alexandre Harari, Camilla Jandus, Michal Bassani-Sternberg* and David Gfeller* (2019). Deep motif deconvolution of HLA-II peptidomes for robust epitope predictions. BioRxiv * Co-corresponding authors.

• Bassani-Sternberg, M. *, Digklia, A., Huber, F., Wagner, D., Sempoux, C., Stevenson, B. J., Thierry, A.-C., Michaux, J., Pak, H., Racle, J., Boudousquie, C., Balint, K., Coukos, G., Gfeller, D., Martin Lluesma, S., Harari, A., Demartines, N., and Kandalaft, L. E.* (2019). A phase Ib study of the combination of personalized autologous dendritic cell vaccine, aspirin and standard of care adjuvant chemotherapy followed by nivolumab for resected pancreatic adenocarcinoma - a proof of antigen discovery feasibility in three patients. Frontiers in Immunology doi:10.3389/fimmu.2019.01832. *Co-corresponding authors

• Ebrahimi-Nik, H., Michaux, J., Corwin, W.L., Keller, G.L., Shcheglova, T., Pak, H., Coukos, G., Baker, B.M., Mandoiu, II, Bassani-Sternberg, M.* and Srivastava, P.K* (2019). Mass spectrometry driven exploration reveals nuances of neoepitope-driven tumor rejection. JCI Insight 5, doi:10.1172/jci.insight.129152. *Co-corresponding authors.

• Chong, C., Marino, F., Pak, H. S., Racle, J., Daniel, R. T., Muller, M., Gfeller, D., Coukos, G., & Bassani-Sternberg, M. (2018). High-throughput and sensitive immunopeptidomics platform reveals profound IFNgamma-mediated remodeling of the HLA ligandome. Mol Cell Proteomics. doi:10.1074/mcp.TIR117.000383

• *Bassani-Sternberg, M., *Braunlein, E., Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., Straub, M., Weber, J., Slotta-Huspenina, J., Specht, K., Martignoni, M. E., Werner, A., Hein, R., D, H. Busch, Peschel, C., Rad, R., Cox, J., Mann, M., & Krackhardt, A. M. (2016). Direct identification of clinically relevant neoepitopes presented on native human melanoma tissue by mass spectrometry. Nat Commun, 7, 13404. doi:10.1038/ncomms13404