Preferentially expressed antigen in melanoma peptide 26-35 presented by Human Leukocyte Antigen A*02:01 (PRAME26-35/HLA-A*02:01)

Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that acts as a repressor of retinoic acid receptor signaling, contributing to the maintenance of a de-differentiated state in cancer cells (PMID: 15901876). The specific decamer peptide SLLMWITQC, corresponding to residues 26–35, is a highly immunogenic epitope that is processed intracellularly and presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01 (PMID: 15843497). This peptide-MHC complex is a prominent target for next-generation immunotherapies because PRAME is overexpressed in a wide variety of solid and hematologic malignancies while remaining largely absent from healthy adult tissues, except for immune-privileged sites like the testis (PMID: 28972059). Current therapeutic strategies targeting this complex primarily involve T-cell receptor (TCR) engineered therapies, such as TCR-T cells and TCR-bispecific molecules, which redirect cytotoxic T cells to recognize and eliminate tumor cells presenting this specific epitope. Clinical trials for agents like IMA203 have demonstrated significant tumor regression in patients with high PRAME-expressing solid tumors who carry the HLA-A*02:01 allele (NCT03686124). However, the development of these therapies requires rigorous screening to avoid cross-reactivity with similar peptides found in vital organs, which could lead to severe off-target toxicity.

Other names

PRAME-004SLLMWITQC-HLA-A*02:01 complexPRAME SLLMWITQC peptideHLA-A2 restricted PRAME antigen

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and tumor cell lysis