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

The Preferentially expressed antigen in melanoma (PRAME) peptide-MHC complex is a significant therapeutic target in oncology, particularly for T-cell based immunotherapies. PRAME is a cancer-testis antigen that is highly expressed in a wide range of malignancies, including melanoma, leukemia, and various solid tumors, while its expression in healthy tissues is largely restricted to the testes, which lack MHC Class I expression [4, 5]. Because PRAME is an intracellular protein, it is not accessible to traditional monoclonal antibodies; instead, it is processed by the proteasome into short peptide fragments, such as the immunodominant SLLQHLIGL decamer, which are then presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 [1, 2]. Therapeutic strategies targeting this complex include T-cell receptor engineered T-cell (TCR-T) therapies and bispecific T-cell engagers (ImmTACs), which are designed to recognize the specific peptide-MHC configuration with high affinity [1, 3]. By binding to this complex, these drugs redirect the immune system to selectively identify and eliminate PRAME-positive malignant cells. Clinical development of these agents has shown promise in treating refractory solid tumors, though challenges remain regarding potential low-level expression in vital organs and the management of immune-related adverse events [1, 2].

Other names

PRAME-HLA-A*02:01 complexMelanoma antigen preferentially expressedMAPEOIP4PRAME-derived peptides

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex followed by T-cell activation and cytotoxic killing of the target cell.