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

The Preferentially Expressed Antigen in Melanoma (PRAME) peptide-HLA-A*02:01 complex is a tumor-specific antigen presentation assembly consisting of a PRAME-derived peptide (most commonly the SLLQHLIGL decamer) bound to the Human Leukocyte Antigen (HLA) A*02:01 molecule (PMID: 15958671). PRAME is a cancer-testis antigen that is highly expressed in a wide range of solid and hematologic malignancies but has restricted expression in normal adult tissues, primarily the testes and ovaries, making it an ideal target for immunotherapy (PMID: 30104729). Because PRAME is an intracellular protein, it cannot be targeted by standard monoclonal antibodies; instead, it must be processed into peptides and presented on the cell surface via MHC Class I molecules for recognition by T-cell receptors (TCRs). This complex is the primary target for several emerging therapeutic modalities, including TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (ImmTACs), which are designed to redirect the immune system to selectively eliminate tumor cells (PMID: 36109515). Clinical candidates such as afamitresgene autoleucel and IMA203 have shown significant efficacy in treating patients with PRAME-positive tumors who carry the HLA-A*02:01 allele (NCT04052334, NCT03686124).

Other names

PRAME-HLA-A2 complexPRAME-A*02:01PRAME pMHCSLLQHLIGL-HLA-A*02:01PRAME-derived peptide-MHC complex

T-cell receptor (TCR) mediated recognition of the specific PRAME peptide (typically SLLQHLIGL) presented by HLA-A*02:01, leading to the formation of an immunological synapse and subsequent T-cell-induced lysis of the tumor cell.