Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma.
Blood Cancer J
; 10(2): 24, 2020 02 28.
Article
em En
| MEDLINE
| ID: mdl-32111817
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Espectrometria de Massas
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Linfócitos T Citotóxicos
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Antígeno de Maturação de Linfócitos B
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Mieloma Múltiplo
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Blood Cancer J
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha