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

The MAGE-A4 peptide presented by HLA-A*02:01 complex is a specialized immunological target used primarily in the development of T-cell receptor (TCR) therapies for solid tumors. MAGE-A4 is a member of the cancer-testis antigen family, which is characterized by high expression in various malignancies but restricted expression in healthy tissues, limited primarily to the immune-privileged germ cells of the testes (PubMed: 30531918). In cancer cells, intracellular MAGE-A4 proteins are degraded by the proteasome into short peptides, such as the GVYDGREHTV decamer, which are then transported to the cell surface and displayed by the Human Leukocyte Antigen (HLA) A*02:01 molecule (Clinical Cancer Research, 2020). This specific peptide-MHC complex serves as a beacon for engineered T-cells, allowing them to selectively identify and destroy tumor cells while sparing normal somatic tissues that lack both MAGE-A4 expression and MHC Class I presentation in the testes. The therapeutic relevance of this target was recently validated by the FDA approval of afamitresgene autoleucel (Tecelra), the first TCR-T cell therapy for synovial sarcoma (FDA, 2024). Ongoing clinical research continues to explore this target across multiple HLA-A*02:01 positive solid tumors, including lung and ovarian cancers, using both cell therapies and bispecific T-cell engagers (Adaptimmune, 2024).

Other names

MAGE-A4/HLA-A2 complexMAGE-A4 p230-239/HLA-A*02:01MAGE-A4-MHC class I complexMAGEA4-HLA-A*02:01GVYDGREHTV/HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the specific MAGE-A4 peptide-HLA complex, leading to T-cell activation, cytokine release, and targeted lysis of tumor cells.