Melanoma-associated antigen 10 peptide presented by Human Leukocyte Antigen A*02 (MAGE-A10/HLA-A*02)

MAGE-A10 peptide presented by HLA-A*02 is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy. MAGE-A10 is a member of the Type I Melanoma Antigen Gene family, classified as a cancer-testis antigen (CTA) because it is expressed in various malignancies but restricted to immune-privileged germ cells in healthy adults (UniProt P43363). The target complex consists of a specific intracellularly processed MAGE-A10 peptide (typically GLYDGREHSV) bound to the HLA-A*02 molecule and displayed on the tumor cell surface. This pMHC is recognized by engineered T-cell receptors (TCRs), facilitating the development of TCR-T cell therapies and bispecific T-cell engagers. Clinical candidates such as ADP-A2M10 have been investigated for treating patients with HLA-A*02-positive tumors that express MAGE-A10, including non-small cell lung cancer, melanoma, and bladder cancer (ClinicalTrials.gov NCT02858310). The therapeutic strategy relies on the tumor-specific presentation of the antigen to provide a wide therapeutic window with minimal on-target, off-tumor toxicity. However, a significant challenge is the potential for off-target cross-reactivity with similar peptides presented on healthy tissues, which requires rigorous preclinical safety profiling (PubMed: 28811304). Patient selection for these therapies requires screening for both the HLA-A*02 allele and the presence of MAGE-A10 mRNA or protein in the tumor tissue.

Other names

MAGE-A10/HLA-A*02 complexMAGE-A10/HLA-A2HLA-A*02:01-restricted MAGE-A10Melanoma antigen family A 10 peptide-MHC

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and tumor cell lysis.