Human leukocyte antigen A*02:01 presenting melanoma-associated antigen A10 peptide (HLA-A*02:01/MAGE-A10)

The HLA-A*02:01 presenting MAGE-A10 peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a target for cancer immunotherapy (Adaptimmune, 2020). MAGE-A10 is a member of the cancer-testis antigen (CTA) family, which is typically expressed in male germ cells but aberrantly expressed in various malignancies, including melanoma, non-small cell lung cancer, and urothelial carcinoma (ClinicalTrials.gov NCT02858310). Because germ cells lack MHC expression, MAGE-A10 is effectively tumor-specific when presented on the cell surface. The HLA-A*02:01 allele is one of the most common MHC Class I molecules, making this specific complex a high-priority target for T-cell receptor (TCR) based therapies (Journal of Immunotherapy of Cancer, 2018). Drugs targeting this complex, such as TCR-engineered T cells (TCR-T), are designed to recognize the specific peptide-HLA configuration and induce a cytotoxic immune response against the tumor. Clinical development has focused on ensuring high specificity to avoid cross-reactivity with other MAGE family members or unrelated proteins in healthy tissues (PubMed: 29351545). Patient selection for these therapies requires screening for both the HLA-A*02:01 genotype and the presence of MAGE-A10 expression in tumor biopsies. This target represents a precision medicine approach to treating solid tumors by leveraging the specificity of the cellular immune system.

Other names

HLA-A2/MAGE-A10MAGE-A10 peptide-HLA-A*02:01 complexMAGE-A10/A2GLYDGREHSV-HLA-A*02:01

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