Preferentially expressed antigen in melanoma (PRAME) (PRAME)

Preferentially expressed antigen in melanoma (PRAME) is a prominent cancer-testis antigen (CTA) that is aberrantly overexpressed in a wide variety of malignancies, including melanoma, non-small cell lung cancer, synovial sarcoma, and acute myeloid leukemia, while remaining largely restricted to the testes and placenta in healthy tissues. It functions as a transcriptional repressor, notably inhibiting retinoic acid receptor (RAR) signaling, which contributes to the maintenance of a proliferative, undifferentiated state in cancer cells. As an intracellular protein, PRAME is targeted via its degradation products—short peptides—that are presented on the cell surface in complex with Major Histocompatibility Complex (MHC) class I molecules. The specific presentation of PRAME peptides by prevalent HLA alleles such as HLA-A*02:01, HLA-A*03:01, and HLA-A*11:01 makes it a versatile target for T-cell receptor (TCR)-based immunotherapies, including TCR-engineered T cells (TCR-T) and bispecific T-cell engagers. These therapies are designed to recognize the peptide-HLA complex with high specificity, triggering a potent cytotoxic immune response against tumor cells. Clinical development of these agents aims to provide treatment options for a broad and diverse patient population by targeting multiple HLA allotypes across different ethnicities.

Other names

PRAMEMAPEOIP4CT130Cancer/testis antigen 130Preferentially expressed antigen in melanoma

T-cell receptor-mediated recognition of peptide-MHC complex, T-cell activation, and perforin/granzyme-mediated cytotoxicity