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

PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that is highly expressed in various malignancies but has limited expression in normal adult tissues, primarily the testis (UniProt P78395). The PRAME peptide–MHC complex consists of specific PRAME-derived peptides, most notably the SLLQHLIGL epitope, presented on the cell surface by Major Histocompatibility Complex (MHC) class I molecules, typically HLA-A*02:01 (PubMed: 15901697). This complex serves as a highly specific target for immunotherapy, including T-cell receptor (TCR)-engineered T cells and bispecific T-cell engagers (Immatics, 2023). By targeting the peptide-MHC complex, these therapies can direct the immune system to recognize and eliminate intracellular proteins that are otherwise inaccessible to traditional antibody-based approaches. Clinical development is currently focused on treating solid tumors and hematological malignancies where PRAME is overexpressed, such as melanoma and sarcoma (PubMed: 34556551). These therapies require patients to be both PRAME-positive and HLA-A*02:01-positive, ensuring precise targeting of the tumor cells.

Other names

PRAME-HLA complexPRAME-HLA-A*02:01MAPEOIP4Preferentially expressed antigen in melanoma

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