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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Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma. / 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.
In: BLOOD CANCER J, Vol. 10, No. 2, 28.02.2020, p. 24.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma
AU - Bilich, Tatjana
AU - Nelde, Annika
AU - Bauer, Jens
AU - Walz, Simon
AU - Roerden, Malte
AU - Salih, Helmut R
AU - Weisel, Katja
AU - Besemer, Britta
AU - Marcu, Ana
AU - Lübke, Maren
AU - Schuhmacher, Juliane
AU - Neidert, Marian C
AU - Rammensee, Hans-Georg
AU - Stevanović, Stefan
AU - Walz, Juliane S
PY - 2020/2/28
Y1 - 2020/2/28
N2 - 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)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.
AB - 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)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.
U2 - 10.1038/s41408-020-0288-3
DO - 10.1038/s41408-020-0288-3
M3 - SCORING: Journal article
C2 - 32111817
VL - 10
SP - 24
JO - BLOOD CANCER J
JF - BLOOD CANCER J
SN - 2044-5385
IS - 2
ER -