Melanoma-associated antigen 10 (MAGE-A10) peptide presented by HLA-A*02:01 or HLA-A*02:06 (MAGE-A10/HLA-A*02)

Melanoma-associated antigen 10 (MAGE-A10) is a member of the MAGE-A family of cancer-testis antigens (CTAs). These proteins are typically expressed only in the testis and placenta, where they are protected from immune recognition, but they become aberrantly expressed in a wide range of cancers, including non-small cell lung cancer (NSCLC), urothelial carcinoma, and melanoma (UniProt P43363). The specific therapeutic target is a processed peptide fragment of MAGE-A10 presented on the cell surface by the Human Leukocyte Antigen (HLA) alleles A*02:01 or A*02:06. This peptide-MHC (pMHC) complex acts as a tumor-specific neoantigen that can be recognized by the immune system. Therapeutic interventions, such as T-cell receptor (TCR) engineered T-cell therapies like ADP-A2M10, are designed to bind this complex with high affinity, leading to the activation of cytotoxic T-cells and the subsequent destruction of the tumor cells (NCT02858310). Clinical application of these therapies requires rigorous patient selection based on both MAGE-A10 expression and the presence of the specific HLA-A*02 restriction elements. A major challenge in targeting this complex is ensuring high specificity to avoid cross-reactivity with similar peptides in vital organs, a lesson learned from previous MAGE-targeting trials (PubMed: 23918359).

Other names

MAGEA10-HLA-A*02 complexMAGE-A10 pMHCMelanoma antigen family A 10 peptide-MHCMAGE-A10/HLA-A2

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