Preferentially expressed antigen in melanoma (PRAME) peptide–HLA-A*02:01 complex (PRAME/HLA-A*02:01)

The PRAME peptide–HLA-A*02:01 complex is a specific cell-surface molecular target formed by the presentation of a peptide fragment (typically the SLLQHLIGL sequence) derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein by the Human Leukocyte Antigen (HLA) allele A*02:01 (Lukat et al., 2023, Frontiers in Oncology). PRAME is a cancer-testis antigen (CTA) that is highly expressed in a wide range of solid and hematological malignancies, including melanoma, uveal melanoma, synovial sarcoma, and acute myeloid leukemia, while its expression in normal tissues is restricted to immune-privileged sites like the testes (Gardsvoll et al., 2022, Cancer Immunology Research). Biologically, PRAME functions as a repressor of retinoic acid receptor (RAR) signaling, thereby inhibiting ligand-induced differentiation and apoptosis in cancer cells (Epping et al., 2005, Cell). Because the PRAME/HLA-A*02:01 complex is uniquely presented on the surface of tumor cells in HLA-A*02:01-positive patients, it serves as an ideal target for T-cell receptor (TCR)-based immunotherapies. Current therapeutic approaches include TCR-engineered T-cell (TCR-T) therapies, such as IMA203, and bispecific T-cell engagers like IMA402, which are designed to bind the complex with high specificity and trigger a potent cytotoxic immune response against the tumor (Immatics, 2024; Medigene, 2023).

Other names

PRAME-A2 complexPRAME SLLQHLIGL peptide-HLA-A*02:01 complexPRAME-HLA-A2PRAME-MHC complex

T-cell receptor (TCR) mediated recognition and redirection of cytotoxic T-lymphocytes to tumor cells