Human leukocyte antigen A*02:01-Melanoma-associated antigen 10 peptide complex (HLA-A*02:01/MAGE-A10)

The Human leukocyte antigen A*02:01-Melanoma-associated antigen 10 peptide complex is a specific molecular target consisting of a peptide fragment derived from the Melanoma-associated antigen 10 (MAGE-A10) presented by the Human Leukocyte Antigen (HLA) allele A*02:01. MAGE-A10 is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in germ cells of the testis but becomes aberrantly expressed in various malignancies, including melanoma, non-small cell lung cancer, and urothelial carcinoma (PMID: 30104351). Because it is not expressed in normal adult somatic tissues, this complex serves as a highly specific target for immunotherapy, particularly T-cell receptor (TCR) therapies. Therapeutic strategies, such as TCR-engineered T-cells like ADP-A2M10, are designed to recognize this specific peptide-MHC combination to induce a targeted immune response against tumor cells (NCT02858310). The clinical utility of this target depends on the patient being HLA-A*02:01 positive and the tumor expressing the MAGE-A10 protein. However, drug development must carefully account for potential cross-reactivity with other MAGE proteins or similar sequences in healthy tissues to avoid severe off-target toxicities, a challenge previously seen in other MAGE-targeted trials (PMID: 23940373).

Other names

MAGE-A10/HLA-A*02:01 complexMAGE-A10 peptide-HLA complexHLA-A2-restricted MAGE-A10 antigenHLA-A*0201 presenting MAGE-A10-derived peptide epitopes

Engineered T-cell receptors (TCRs) recognize the specific peptide-HLA complex on the surface of tumor cells, leading to T-cell activation, cytokine release, and direct lysis of the target cell.