Multiple myeloma-associated tumor-associated antigens presented on MHC molecules (MM-TAAs)

Tumor-associated antigens (TAAs) presented on Major Histocompatibility Complex (MHC) molecules of myeloma cells are a diverse group of intracellularly derived peptides that serve as critical targets for T-cell-based immunotherapies. In multiple myeloma, these antigens frequently include cancer-testis antigens such as NY-ESO-1, MAGE-A3, and PRAME, which are highly expressed in malignant plasma cells but absent in most healthy adult tissues (Rapoport et al., 2015, Nature Medicine). These peptides are processed by the proteasome and loaded onto MHC Class I molecules, most commonly HLA-A*02:01, for presentation to CD8+ T-cells (Walz et al., 2015, Blood). Therapeutic interventions such as T-cell receptor (TCR) engineered T-cells and peptide vaccines are designed to recognize these specific HLA-peptide complexes to induce a potent anti-tumor immune response (Lulla et al., 2016, Blood). Unlike CAR-T cells which target surface proteins like BCMA, TCR-based therapies can access the vast landscape of the intracellular proteome. However, the efficacy of targeting these antigens can be limited by HLA downregulation, a common immune escape mechanism in myeloma, and the risk of off-target toxicity if the target peptide shares homology with proteins in vital organs. Monitoring HLA status and specific antigen expression levels is essential for patient selection and predicting treatment success (ClinicalTrials.gov, NCT03391778).

Other names

Myeloma-associated antigensHLA-peptide complexes in myelomaMyeloma immunopeptidomeMHC-restricted myeloma antigensCancer-testis antigens in myeloma

T-cell receptor (TCR) mediated recognition of specific peptide-MHC complexes on the surface of myeloma cells, leading to T-cell activation, cytokine release, and granzyme/perforin-mediated lysis of the target cell.