Melanoma-associated antigen A4 peptide presented by human leukocyte antigen A2 (MAGE-A4/HLA-A2 complex)

The **MAGE-A4 peptide presented by HLA-A2** is a molecular complex consisting of a peptide fragment derived from the melanoma-associated antigen A4 (MAGE-A4), a cancer-testis antigen, bound to the major histocompatibility complex class I molecule human leukocyte antigen A2 (HLA-A2) on the cell surface. This specific complex is recognized by T cell receptors (TCRs) on cytotoxic T lymphocytes, enabling immune targeting of tumor cells expressing MAGE-A4 in the context of HLA-A2. MAGE-A4 is aberrantly expressed in a range of solid tumors—including synovial sarcoma, lung cancer, melanoma, and others—but is minimally present in healthy adult tissues, typically restricted to immune-privileged sites such as the testis[1][3][4][6]. Engineered therapies, including TCR-transduced T cells (such as afamitresgene autoleucel), bispecific T cell engagers, and peptide vaccines, specifically target this peptide-MHC complex to induce tumor cell killing[1][3][7]. Patient eligibility for treatment is determined by both the expression of MAGE-A4 in the tumor and the presence of an HLA-A2 allele, making both features essential biomarkers for therapy selection[1][5]. The safety of targeting this complex depends on ensuring the absence of MAGE-A4 in vital normal tissues to minimize off-tumor toxicity[1][5][7].

Other names

MAGE-A4 peptide/HLA-A2MAGEA4/HLA-A2MAGEA4 230–239/HLA-A2Melanoma-associated antigen 4 peptide/HLA-A2cancer-testis antigen MAGE-A4 peptide presented by HLA-A2

Recognition by engineered T cell receptors (TCRs) on adoptive cell therapies leading to cytotoxic killing of tumor cells presenting MAGE-A4/HLA-A2 on their surface; Stimulation of tumor-specific T cell responses via vaccination; Engagement of immune effector cells by bispecific T cell engagers targeting the complex