Melanoma-associated antigen 1 peptide epitope presented on HLA-A*02:01 (MAGE-A1/HLA-A*02:01)

Melanoma-associated antigen 1 (MAGE-A1) is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in the immune-privileged testis but aberrantly expressed in various solid and hematological malignancies [1, 4, 17]. The specific target is the complex formed by a MAGE-A1-derived peptide, most commonly the nine-amino acid sequence KVLEYVIKV (residues 278-286), and the Human Leukocyte Antigen (HLA) allele A*02:01 [1, 2, 11]. This peptide-MHC (pMHC) complex is presented on the surface of tumor cells, making it a highly specific target for immunotherapy [4, 6, 13]. Therapeutic strategies primarily involve T-cell receptor (TCR) engineered T-cell (TCR-T) therapies, such as IMA202, TK-8001, and TSC-204-A0201, which are designed to recognize this specific complex and induce tumor cell lysis [4, 7, 8, 11]. Because MAGE-A1 is not expressed in normal somatic tissues and the testis lacks HLA expression, the risk of on-target, off-tumor toxicity is significantly minimized [13, 17]. Clinical trials have demonstrated the feasibility of targeting this complex in patients with melanoma, hepatocellular carcinoma, and multiple myeloma [4, 11, 14]. Efficacy is often monitored through biomarkers such as MAGE-A1 expression levels in tumor biopsies and the persistence of engineered T cells in the peripheral blood [4, 11, 18]. However, challenges remain, including potential cross-reactivity with similar peptides in healthy tissues and the loss of HLA expression by tumor cells as a resistance mechanism [15, 21].

Other names

MAGE-A1/HLA-A*02:01 complexMAGE-A1 (278-286) peptideKVLEYVIKV/HLA-A*02:01Melanoma-associated antigen 1 peptide-MHC complexMAGE-A1-A2

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex on the tumor cell surface, leading to cytotoxic T-lymphocyte (CTL) activation, cytokine release, and tumor cell lysis [4, 7, 11].