Identification of HLA-restricted Cytotoxic T Lymphocyte Epitopes of B Cell Maturation Antigen as Promising Peptide Vaccine Candidates for Preventive and Therapeutic Strategies in Multiple Myeloma

Abstract

Multiple myeloma (MM) is an incurable hematologic malignancy for which curative treatment remains elusive. Consequently, immunotherapeutic strategies that selectively induce MM-specific T cell responses by targeting MM-associated antigens have emerged. This study aims to identify HLA-restricted cytotoxic T lymphocyte (CTL) epitopes derived from B cell maturation antigen (BCMA) as potential peptide vaccine candidates to advance preventive and therapeutic interventions for MM. BCMA expression in bone marrow tissue samples from 96.8% of MM patients is observed, and the positive membrane BCMA expression is associated with inferior overall survival outcomes. Through an in silico model, four BCMA epitope peptides that exhibit in vitro concentration-dependent binding to the HLA*A11:01 molecule are identified. Comparative analyses reveal that BCMA-specific CTLs stimulated by BCMA-2, BCMA-3, and BCMA-4 peptides exhibit significantly greater cytolysis of cancer cells, including BCMA-overexpressing KMS-20 and KKU-055 cells, in comparison to an unpulsed condition or an irrelevant control peptide derived from human immunodeficiency virus-1 (HIV-1). Moreover, the observed cytolytic activities of these CTLs are significantly distinct when compared to corresponding BCMA-negative cells, thereby indicating antigen-specificity. This study highlights the promising potential of utilizing immunogenic HLA-A*11:01-restricted BCMA peptides as a viable approach for cancer vaccination and T cell-based therapy in the context of MM.