Melanoma-associated antigen A4 peptide–Human leukocyte antigen class I complex (MAGEA4–HLA complex)

The Melanoma-associated antigen A4 (MAGEA4) peptide–Human leukocyte antigen (HLA) class I complex is a specific molecular target for cancer immunotherapy, particularly T-cell receptor (TCR) based therapies [1, 2]. MAGE-A4 is a member of the cancer-testis antigen (CTA) family, which is normally expressed only in the immune-privileged environment of the testes and is absent from other healthy adult tissues [3]. However, MAGE-A4 is frequently overexpressed in various solid tumors, including synovial sarcoma, myxoid/round cell liposarcoma, and non-small cell lung cancer [1, 5]. In these cancer cells, MAGE-A4 proteins are processed into short peptides, such as the GVYDGREHTV decamer, which are then presented on the cell surface by HLA class I molecules, most commonly HLA-A*02:01 [2, 4]. This presentation allows engineered TCR-T cells or bispecific TCR molecules to recognize and selectively eliminate the malignant cells [1, 4]. The clinical significance of this target was highlighted by the 2024 FDA approval of afamitresgene autoleucel, the first TCR-T cell therapy, which specifically targets this complex in patients with advanced synovial sarcoma [1].

Other names

MAGE-A4/HLA-A*02 complexMAGE-A4/HLA-A2 complexMAGEA4-HLA-A*02:01MAGE-A4 peptide-MHC complexGVYDGREHTV-HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and tumor cell lysis.