PRAME-derived peptide-HLA class I complex (PRAME/HLA-I)

PRAME (Preferentially Expressed Antigen in Melanoma) is a member of the cancer-testis antigen (CTA) family, characterized by high expression in various malignancies and limited expression in normal adult tissues, primarily the testes and ovaries. The target "PRAME-derived peptide presented by HLA class I" refers to the complex formed when intracellular PRAME protein is processed by the proteasome into short peptides (e.g., SLLQHLIGL or ALYVDSLFFL) and presented on the cell surface by Human Leukocyte Antigen (HLA) class I molecules, most commonly HLA-A*02:01. This peptide-MHC (pMHC) complex acts as a specific ligand for T-cell receptors (TCRs), making it an ideal target for T-cell-based immunotherapies. Therapeutic modalities targeting this complex include TCR-engineered T-cell (TCR-T) therapies like IMA203, bispecific T-cell engagers (TCEs) like IMC-F106C, and TCR-mimic (TCRm) antibodies. These therapies aim to redirect the immune system to recognize and kill PRAME-expressing tumor cells across multiple indications, including melanoma, sarcoma, and acute myeloid leukemia. While highly selective, potential safety concerns include cytokine release syndrome (CRS) and the risk of off-target cross-reactivity with similar peptides in healthy tissues.

Other names

PRAME-HLA complexPRAME pMHCPRAME-derived peptide-MHC class I complexPRAME/HLA-A*02:01 complexPRAME/HLA-A2 complexPRAME-004 peptide-HLA complex

T-cell redirection, T-cell receptor (TCR) mediated cell killing, Antibody-dependent cellular cytotoxicity (ADCC)