Publikation

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

Wissenschaftlicher Artikel/Review - 28.02.2020

Bereiche
PubMed
DOI

Zitation
Bilich T, Stevanovic S, Rammensee H, Neidert M, Schuhmacher J, Lübke M, Marcu A, Besemer B, Weisel K, Salih H, Roerden M, Walz S, Bauer J, Nelde A, Walz J. Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma. Blood Cancer J 2020; 10:24.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Blood Cancer J 2020; 10
Veröffentlichungsdatum
28.02.2020
eISSN (Online)
2044-5385
Seiten
24
Kurzbeschreibung/Zielsetzung

The 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). Additionally, P(BCMA) was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA) 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) in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA)-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) using patient-derived P(BCMA)-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.