Human leukocyte antigen A*01:01 presenting melanoma-associated antigen 3-derived peptide (HLA-A*01:01/MAGE-A3)

The HLA-A*01:01 presenting MAGE-A3-derived peptide complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various cancer cells. MAGE-A3 (Melanoma-associated antigen 3) is a member of the cancer-testis antigen family, which is typically expressed only in male germ cells and aberrantly in various malignancies, including melanoma, non-small cell lung cancer, and head and neck cancers (PMID: 24048793). The specific peptide sequence, often EVDPIGHLY, is processed and presented by the HLA-A*01:01 allele, making it a highly specific target for T-cell receptor (TCR) based immunotherapies (PMID: 7507011). Targeting this complex allows the immune system to selectively recognize and eliminate tumor cells while sparing most healthy tissues. However, therapeutic development has faced significant challenges due to off-target, off-tumor toxicity. Most notably, cross-reactivity with the muscle protein Titin led to severe cardiotoxicity in early clinical trials (PMID: 23765109). Current research focuses on engineering TCRs with higher specificity and safety profiles to exploit this potent tumor-specific antigen. This target remains a high-priority candidate for TCR-T and bispecific T-cell engager (BiTE) platforms.

Other names

MAGE-A3/HLA-A*01:01 complexMAGE-A3:168-176/HLA-A1EVDPIGHLY/HLA-A*01:01MAGE-A3-A1 complex

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) activation leading to tumor cell lysis.