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

The PRAME-derived peptide–Human leukocyte antigen (HLA) complex is a tumor-associated antigen target consisting of a specific peptide fragment from the Preferentially Expressed Antigen in Melanoma (PRAME) protein presented on the cell surface by HLA class I molecules, most frequently HLA-A*02:01 (PubMed PMID: 33093345). PRAME is a member of the cancer-testis antigen family and normally functions as a repressor of retinoic acid receptor (RAR) signaling, which can inhibit cell differentiation and promote oncogenesis (PubMed PMID: 15701701). While PRAME is highly expressed in various malignancies—including melanoma, uveal melanoma, synovial sarcoma, and certain leukemias—its expression in healthy adult tissues is restricted to the testis and low levels in the adrenal glands and ovaries, providing a therapeutic window for targeting (PubMed PMID: 28923844). Immunotherapeutic approaches targeting this complex include T-cell receptor (TCR) engineered T-cells, such as IMA203, and bispecific T-cell engagers like IMA402, which are designed to recognize the peptide-HLA complex with high affinity (Immatics.com). These therapies aim to trigger a potent T-cell mediated cytotoxic response specifically against tumor cells. Clinical trials are currently evaluating the safety and efficacy of these agents in patients whose tumors demonstrate high PRAME expression and who carry the appropriate HLA allele (ClinicalTrials.gov).

Other names

PRAME-MHC complexPRAME peptide-HLA-A*02 complexPRAME-HLA-A2Antigen PRAME-HLA complexPRAME-derived peptide-MHC class I complex

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