Myeloperoxidase (132-140) peptide presented by Human Leukocyte Antigen A*02:01 (MPO132-140/HLA-A*02:01)

The Myeloperoxidase (132-140) peptide presented by Human Leukocyte Antigen A*02:01 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for immunotherapy in myeloid malignancies (Schetelig et al., 2008). Myeloperoxidase (MPO) is a heme-containing enzyme primarily expressed in the primary granules of myeloid cells and is frequently overexpressed in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and occasionally multiple myeloma (Lichtenegger et al., 2019). The peptide fragment RLFEQHGLL, spanning residues 132 to 140 of the MPO protein, is processed intracellularly and presented on the cell surface by the HLA-A*02:01 allele, the most common MHC class I molecule in many populations (Medigene AG, 2021). This pMHC complex is recognized by specific T-cell receptors (TCRs), enabling the development of TCR-engineered T-cell therapies such as MDG1011 (Wermke et al., 2021). By targeting this complex, these therapies aim to induce cytotoxic T-lymphocyte-mediated lysis of leukemic cells while minimizing damage to non-myeloid tissues. However, because MPO is also expressed in healthy myeloid precursors, a significant therapeutic challenge is the risk of on-target, off-tumor myelotoxicity leading to prolonged cytopenias (Medigene AG, 2021). Patient selection for such therapies requires screening for both the HLA-A*02:01 genotype and high MPO expression in tumor cells (NCT03503968).

Other names

MPO-A2 complexRLFEQHGLL-HLA-A*02:01 complexMPO(132-140)/HLA-A*02:01Myeloperoxidase-derived peptide 132-140 in complex with HLA-A*02:01

Recognition by engineered T-cell receptors (TCRs) leading to cytotoxic T-lymphocyte activation and tumor cell lysis.