Preferentially expressed antigen in melanoma peptide–major histocompatibility complex (PRAME-MHC)

Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen (CTA) that is frequently overexpressed in hematological malignancies like acute myeloid leukemia (AML) and various solid tumors, while showing minimal expression in healthy tissues except for the testis and ovaries (UniProt P78395). The PRAME peptide–MHC complex forms when intracellular PRAME proteins are degraded by the proteasome into specific peptides, such as VLDGLDVLL, which are then loaded onto Major Histocompatibility Complex (MHC) Class I molecules, typically HLA-A*02:01, and presented on the cell surface (Greiner et al., 2006, Blood). Biologically, PRAME functions as a repressor of retinoic acid receptor (RAR) signaling, which prevents cell differentiation and promotes the survival of leukemic blasts (Epping et al., 2005, Cell). This peptide-MHC complex is a primary target for TCR-based immunotherapies, including TCR-engineered T-cells (TCR-T) and bispecific T-cell engagers, which provide a mechanism for highly specific recognition of tumor cells (Immatics, 2023). Clinical candidates like IMA203 and MDG1011 are designed to bind this complex to induce T-cell mediated lysis of PRAME-expressing leukemia and cancer cells (ClinicalTrials.gov NCT03686124). The therapeutic success of targeting this complex depends on both the density of the peptide-MHC presentation and the patient's HLA genotype.

Other names

PRAME-HLA-A*02 complexPRAME-MHC class I complexPRAME-HLA complexPRAME-peptide-HLA-A*02:01 complex

T-cell receptor (TCR) mediated recognition and cytotoxic killing of cells presenting PRAME peptides on MHC Class I.