Preferentially expressed antigen in melanoma peptide–HLA class I complex (PRAME-HLA-I)

The PRAME peptide–HLA class I complex is a specific molecular target formed by the presentation of peptides derived from the Preferentially Expressed Antigen in Melanoma (PRAME) protein on the surface of cells via Human Leukocyte Antigen (HLA) class I molecules, most commonly HLA-A*02:01 (PMID: 35914154). PRAME is a member of the cancer-testis antigen family, meaning it is highly expressed in a wide variety of solid and hematologic malignancies—including melanoma, uveal melanoma, and acute myeloid leukemia—while remaining largely absent from healthy adult tissues, except for the testis and low levels in the adrenals and ovaries (PMID: 28923890). This restricted expression pattern makes the PRAME-HLA complex an ideal target for T-cell receptor (TCR) based therapies, such as TCR-engineered T-cells (TCR-T) and TCR-bispecific engagers (PMID: 33033171). These therapeutic modalities, such as IMA203 and IMC-F106C, are designed to recognize the specific peptide-HLA configuration with high affinity, triggering a potent cytotoxic immune response against the tumor cells (Immatics, 2023; Immunocore, 2023). Clinical development of drugs targeting this complex is ongoing, with several candidates showing promising efficacy in early-phase trials for multiple cancer types. The complex is unique because it allows the immune system to recognize an intracellular protein that would otherwise be invisible to traditional antibody-based therapies. Successful targeting requires both the presence of the PRAME protein and the specific HLA allele capable of presenting the immunogenic peptide.

Other names

PRAME-MHC complexPRAME-HLA-A*02:01 complexPRAME/HLA-A2PRAME-pMHCPreferentially expressed antigen in melanoma-HLA complex

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