Preferentially expressed antigen in melanoma (PRAME) (PRAME)

Preferentially expressed antigen in melanoma (PRAME) is a prominent cancer-testis antigen (CTA) that is highly expressed in various malignancies but has limited expression in normal adult tissues, primarily the testis, ovary, and adrenal glands (UniProt P78395). Biologically, PRAME acts as a dominant-negative repressor of retinoic acid receptor (RAR) signaling, thereby inhibiting RAR-mediated differentiation, cell cycle arrest, and apoptosis, which contributes to the maintenance of a malignant phenotype (PMID: 15703771). Because PRAME is an intracellular protein, it is targeted via its processed peptides presented on the cell surface by Human Leukocyte Antigen (HLA) molecules, most commonly HLA-A*02:01 (PMID: 28972055). Due to its high tumor specificity and immunogenicity, PRAME is a major target for immunotherapy, particularly for T-cell receptor (TCR)-based therapies and bispecific molecules (PMID: 30033263). Current therapeutic strategies include TCR-engineered T-cells (e.g., IMA203) and ImmTAC molecules (e.g., IMC-F10V) which redirect the immune system to eliminate PRAME-positive cancer cells. Its role as a biomarker is also significant in the diagnosis of melanoma and the prognosis of uveal melanoma and certain leukemias (PMID: 34181063).

Other names

Melanoma antigen preferentially expressed in tumorsMAPEOIP4OPA-interacting protein 4Cancer/testis antigen 130CT130

T-cell receptor (TCR) engineered T-cell therapy, bispecific T-cell engagers (BiTEs), and peptide-based therapeutic vaccines designed to recognize PRAME-derived peptides presented on HLA class I molecules.