Melanoma-associated antigen 1 peptide presented on HLA-A*02:01 or HLA-C*07:02 (MAGE-A1/HLA-A*02:01 or HLA-C*07:02)

Melanoma-associated antigen 1 (MAGE-A1) is a prominent member of the cancer-testis antigen (CTA) family, which is typically expressed only in the immune-privileged environment of the male germline but becomes aberrantly re-expressed in various malignancies [10, 15]. In tumor cells, MAGE-A1-derived peptides, such as the KVLEYVIKV epitope, are processed and presented on the cell surface by specific Major Histocompatibility Complex (MHC) Class I molecules, including HLA-A*02:01 and HLA-C*07:02 [1, 18]. This peptide-MHC (pMHC) complex serves as a highly specific therapeutic target for T-cell receptor (TCR) engineered T-cell (TCR-T) therapies, which are designed to recognize the complex and trigger a cytotoxic immune response against the cancer cell [6, 16]. Biologically, MAGE-A1 functions as a transcriptional corepressor and has been shown to inhibit p53-mediated apoptosis, thereby contributing to tumor cell survival and chemoresistance [12, 14]. Several investigational drugs, including TSC-204-A0201, TSC-204-C0702, TK-8001, and IMA202, are currently in clinical development to target these specific pMHC complexes in patients with solid tumors like melanoma and non-small cell lung cancer [1, 2, 3]. A significant therapeutic challenge is the potential for tumor escape through HLA loss of heterozygosity (LOH), where the tumor loses the specific HLA allele required for antigen presentation [13, 21]. Additionally, safety monitoring is critical for these therapies to manage risks such as cytokine release syndrome (CRS) and potential off-target cross-reactivity with other proteins in the MAGE family [14, 16].

Other names

MAGE-A1/HLA-A*02:01 complexMAGE-A1/HLA-C*07:02 complexMAGE-A1 pMHCMelanoma-associated antigen 1 peptide-MHC complexMAGE-A1/HLA-A2MAGE-A1/HLA-C7

Targeted cell-mediated cytotoxicity via engineered T-cell receptor recognition of peptide-MHC complex