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Bilich, Tatjana; Nelde, Annika; Bauer, Jens; Walz, Simon; Roerden, Malte; Salih, Helmut R.; Weisel, Katja; Besemer, Britta; Marcu, Ana; Lübke, Maren; Schuhmacher, Juliane; Neidert, Marian C.; Rammensee, Hans-Georg; Stevanović, Stefan; Walz, Juliane S.

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

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  • Media type: E-Article
  • Title: Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma
  • Contributor: Bilich, Tatjana; Nelde, Annika; Bauer, Jens; Walz, Simon; Roerden, Malte; Salih, Helmut R.; Weisel, Katja; Besemer, Britta; Marcu, Ana; Lübke, Maren; Schuhmacher, Juliane; Neidert, Marian C.; Rammensee, Hans-Georg; Stevanović, Stefan; Walz, Juliane S.
  • Published: Springer Science and Business Media LLC, 2020
  • Published in: Blood Cancer Journal, 10 (2020) 2
  • Language: English
  • DOI: 10.1038/s41408-020-0288-3
  • ISSN: 2044-5385
  • Origination:
  • Footnote:
  • Description: AbstractThe B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18-restricted ligand P(BCMA)B*18. Additionally, P(BCMA)B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA)B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8+ T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA)B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA)B*18-specific CD8+ T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA)B*18 using patient-derived P(BCMA)B*18-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.
  • Access State: Open Access