Mapping the Impact of Proteasome Inhibitor Therapy on the Immunopeptidome of Multiple Myeloma: Mass Spectrometry Identifies Robust Targets for T Cell Immunotherapy

Recent studies underscore that multiple myeloma is an immunogenic disease and suggest that it can be effectively treated by T cell based immunotherapy via immunomodulation. This strategy might be synergistically complemented by therapeutic vaccination, which may help induce and guide specific anti-cancer T cell responses. We have recently conducted a study which directly characterized the antigenic landscape of myeloma by mass spectrometric analysis of naturally presented HLA ligands and identified a panel of T cell epitopes characterized by exquisite myeloma-association (Walz, Stickel et. al., Blood 2015). As standard of care in myeloma includes proteasome inhibitor therapy and the proteasome plays a central role in the generation of MHC-presented peptides, it is of great importance to thoroughly characterize and take into account the effects of this treatment on the antigenic landscape of myeloma cells and implement only robustly presented targets for peptide vaccine design. This is even more important