Melanoma-associated antigen A4 (MAGE-A4) peptide presented by Human leukocyte antigen A*02:01 (HLA-A*02:01) (MAGE-A4/HLA-A*02:01)

The Melanoma-associated antigen A4 (MAGE-A4) peptide presented by Human leukocyte antigen A*02:01 (HLA-A*02:01) is a tumor-specific antigen complex consisting of a processed fragment of the MAGE-A4 protein bound to the HLA-A*02:01 molecule. MAGE-A4 belongs to the cancer-testis antigen (CTA) family, which is typically expressed only in immune-privileged germ cells of the testes but becomes highly expressed in various solid tumors, such as synovial sarcoma, myxoid/round cell liposarcoma, and non-small cell lung cancer (UniProt: P43358). The specific peptide sequence, GVYDGREHTV, is presented on the cell surface, making it a highly specific target for engineered T-cell receptor (TCR) therapies (PubMed: 33434183). Drugs like afamitresgene autoleucel (Tecelra) utilize engineered TCRs to specifically recognize this pMHC complex, leading to the activation of T-cells and the subsequent destruction of tumor cells (FDA: 2024). This target is particularly valuable because its expression is largely absent in healthy adult somatic tissues, reducing the likelihood of on-target, off-tumor toxicity. Clinical efficacy is contingent upon the patient possessing the HLA-A*02:01 allele and the tumor demonstrating sufficient MAGE-A4 expression levels.

Other names

MAGE-A4/HLA-A2 complexMAGEA4-HLA-A*02:01GVYDGREHTV-HLA-A*02:01MAGE-A4 pMHC

T-cell receptor (TCR) mediated recognition and subsequent T-cell activation and tumor cell lysis