Melanoma-associated antigen A4 peptide–HLA-A*02:01 complex (MAGE-A4–HLA-A*02:01)

The **MAGE-A4 peptide antigen presented on HLA-A*02:01** is a tumor-specific immune target formed by intracellular processing of the melanoma-associated antigen A4 (MAGE-A4), a cancer-testis antigen. MAGE-A4 is minimally expressed in normal tissue (restricted to testis and placenta), but is frequently overexpressed in a broad spectrum of solid tumors, including synovial sarcoma, liposarcoma, bladder, head and neck, lung, esophageal, and breast cancers, among others[2][4][6][7]. The antigenic peptide (most commonly GVYDGREHTV, residues 230–239) is presented on the tumor cell surface by the MHC class I molecule HLA-A*02:01, making the complex specifically recognizable by cytotoxic T lymphocytes and engineered T cell therapies (such as afamitresgene autoleucel). This complex has become a prime target for adoptive cell therapies—including TCR-T and CAR-T cell approaches—and peptide vaccines due to its tumor specificity and immunogenic potential[1][3][5][7]. The primary therapeutic challenge is ensuring highly specific recognition to avoid off-target effects and monitoring immune-related toxicities[3][7]. Expression of both the antigen and the correct HLA allele are essential biomarkers for patient selection and efficacy.

Other names

MAGE-A4–pMHCMAGE-A4/HLA-A*02:01MAGEA4 peptide–HLA-A2MAGE-A4 230-239/HLA-A2MAGE-A4–peptide–HLA complex

Targeted T cell killing: Cytotoxic T lymphocytes or TCR-engineered T cells specifically recognize and lyse tumor cells expressing the MAGE-A4 peptide presented on HLA-A*02:01[3][7][5]. Immune activation: Peptide vaccines or adoptive T cell therapies elicit targeted immune responses against cells presenting the complex. Potential combination with checkpoint inhibitors for synergy, though the complex itself is not a checkpoint molecule[7].