Preferentially expressed antigen in melanoma peptide–Human leukocyte antigen complex (PRAME-HLA complex)

The Preferentially expressed antigen in melanoma (PRAME) peptide–Human leukocyte antigen (HLA) complex is a specific peptide-MHC (pMHC) target used in cancer immunotherapy. PRAME is a cancer-testis antigen (CTA) that is highly expressed in various malignancies, including melanoma, non-small cell lung cancer, and acute myeloid leukemia, but has restricted expression in normal tissues, primarily the testis (UniProt P78395). Intracellular PRAME protein is processed by the proteasome into short peptides, such as the immunodominant SLLMWITQC epitope, which are then presented on the cell surface by HLA class I molecules, most notably HLA-A*02:01 (PubMed: 15705856). This complex is recognized by specific T-cell receptors (TCRs), enabling the development of TCR-engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (PubMed: 33020240). Because PRAME is an intracellular protein, the pMHC complex is the only way for the immune system to target it, making it a critical focus for treating "undruggable" intracellular oncogenic targets. Current clinical candidates like IMA203 and IMA402 specifically target this complex to induce T-cell mediated destruction of tumor cells (ClinicalTrials.gov: NCT03686124).

Other names

MAPEOIP4PRAME-MHC complexPRAME/HLA-A*02 complexPreferentially expressed antigen in melanoma presented by HLA-A*02

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation, secretion of cytotoxic granules such as perforin and granzyme, and induction of apoptosis in the target tumor cell (PubMed: 33020240).