Melanoma antigen preferentially expressed in tumors (PRAME) (PRAME)

Melanoma antigen preferentially expressed in tumors (PRAME) is a prominent cancer-testis antigen (CTA) that is highly expressed in a wide range of hematological and solid tumors, including melanoma, leukemia, and lung cancer, while remaining largely absent in healthy adult tissues except for the testis (UniProt: P78395). Functionally, PRAME acts as a repressor of retinoic acid receptor (RAR) signaling by binding to RAR in the presence of retinoic acid, which prevents the recruitment of co-activators and inhibits cell differentiation and apoptosis (PubMed: 15034584). It also serves as a substrate recognition component of a Cullin-RING E3 ubiquitin ligase complex, contributing to the degradation of specific cellular proteins (PubMed: 23354166). Because PRAME-derived peptides are presented on the cell surface by HLA molecules, it has become a high-priority target for T-cell receptor (TCR)-engineered T-cell therapies, such as IMA203 and MDG1011, which are designed to recognize and eliminate PRAME-positive tumor cells (ClinicalTrials.gov: NCT03686124). Additionally, PRAME expression is utilized as a diagnostic and prognostic biomarker, particularly in distinguishing between benign nevi and malignant melanoma and in predicting metastasis in uveal melanoma (PubMed: 28710138).

Other names

Preferentially expressed antigen in melanomaMAPEOIP4Cancer/testis antigen 130CT130

T-cell receptor (TCR) engineered T-cell therapy targeting PRAME peptide-HLA complexes and therapeutic vaccination to induce PRAME-specific immune responses.