Human leukocyte antigen A*02:01 presenting melanoma-associated antigen 1 peptide (HLA-A*02:01/MAGE-A1)

The Human leukocyte antigen A*02:01 presenting melanoma-associated antigen 1 peptide (specifically the KVLEYVIKV epitope) is a peptide-major histocompatibility complex (pMHC) class I target used in cancer immunotherapy (Cancer Res. 2001;61:4072–7; NIH). MAGE-A1 is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in male germ cells and various malignant tumors, making it a highly specific target for T-cell mediated therapy (Immatics; T-knife Therapeutics). The complex is formed when the intracellularly processed MAGE-A1 protein is loaded onto the HLA-A*02:01 allele and presented on the cell surface for recognition by CD8+ T-cells (J Immunol. 2002;169:575-80). Therapeutic strategies targeting this complex include T-cell receptor-engineered T-cell (TCR-T) therapies, such as IMA202 and TK-8001, which utilize high-affinity TCRs to recognize the pMHC and induce cytotoxic T-lymphocyte (CTL) responses against tumor cells (NIH; CGTlive). These therapies are currently being evaluated in clinical trials for patients with MAGE-A1-positive solid tumors, including melanoma and hepatocellular carcinoma (Immudex). Clinical challenges include potential off-target cross-reactivity with similar peptides in healthy tissues and tumor evasion through HLA loss of heterozygosity (TScan Therapeutics). Monitoring for cytokine release syndrome and neurotoxicity is essential during treatment with these engineered cell products (NIH).

Other names

MAGE-A1:HLA-A*02:01MAGE-A1/A2 complexHLA-A2/MAGE-A1MAGE-A1 278-286 peptide-MHC complexHLA-A*0201 presenting MAGE-A1 peptide

T-cell receptor-engineered T-cell (TCR-T) therapy involves the adoptive transfer of T-cells modified to express a TCR specific for the MAGE-A1/HLA-A*02:01 complex, resulting in MHC-restricted recognition and cytotoxic lysis of tumor cells.