Major histocompatibility complex class I and II molecules presenting melanoma-associated antigen 10 peptide epitopes (HLA-MAGE-A10)

Melanoma-associated antigen 10 (MAGE-A10) is a cancer-testis antigen (CTA) that is aberrantly expressed in various solid tumors, including melanoma, lung, and bladder cancers, while remaining silent in healthy tissues except for the immune-privileged testes and placenta (UniProt: P43363). The therapeutic target is the complex formed when MAGE-A10 protein is processed into short peptide fragments and presented on the cell surface by Major Histocompatibility Complex (MHC) class I or II molecules, such as HLA-A*02:01 (PubMed: 28972055). This peptide-MHC complex acts as a specific marker for malignant cells, allowing the immune system to distinguish them from normal cells. Drugs targeting this complex, such as engineered T-cell receptor (TCR) therapies like ADP-A2M10, are designed to bind specifically to the MAGE-A10 peptide within the MHC groove to trigger a cytotoxic immune response (ClinicalTrials.gov: NCT02858310). Because the testes lack MHC expression, the risk of on-target toxicity is reduced, making it an attractive target for immunotherapy. However, challenges include ensuring the TCR does not cross-react with other MAGE family members or similar peptides found in healthy tissues like the brain or heart (PubMed: 30224700). Clinical development has focused on HLA-A*02 restricted epitopes, though MHC class II presentation also plays a role in broader immune recognition (PubMed: 11007340).

Other names

MAGE-A10 peptide-MHC complexMAGE-A10-HLA complexMelanoma-associated antigen 10-MHC complexHLA-A*02:01/MAGE-A10

T-cell receptor (TCR) mediated recognition and cytotoxic T-lymphocyte activation