Preferentially expressed antigen in melanoma (PRAME) ALYVDSLFFL peptide in complex with HLA-A*02 (PRAME-ALY-HLA-A*02)

The PRAME ALY peptide in complex with HLA-A*02 is a peptide-major histocompatibility complex (pMHC) that serves as a highly specific target for cancer immunotherapy (Kessler et al., 2001, PMID: 11418639). The PRAME (Preferentially Expressed Antigen in Melanoma) protein is a cancer-testis antigen (CTA) that is overexpressed in a wide range of solid tumors, including melanoma, sarcoma, and lung cancer, while remaining largely absent in healthy adult tissues except for the testis (Gnjatic et al., 2006, PMID: 16551862). The ALY peptide (sequence ALYVDSLFFL) is a specific 10-mer epitope derived from PRAME that is processed and presented on the cell surface by the HLA-A*02:01 molecule. This pMHC complex is the primary target for several next-generation immunotherapies, including TCR-engineered T-cell (TCR-T) therapies like IMA203 and TCR-bispecific engagers like IMC-P115C (Schuster et al., 2022, PMID: 35641564). These therapeutic agents are designed to bind the PRAME-ALY-HLA complex with high affinity, triggering T-cell activation and the subsequent lysis of tumor cells. Clinical trials have demonstrated that targeting this complex can lead to objective responses in patients with heavily pretreated solid tumors (NCT03686124). Patient selection for these therapies typically requires confirmation of both HLA-A*02:01 genotype and PRAME expression in the tumor tissue. Potential safety concerns include cytokine release syndrome and the risk of off-target reactivity if the TCR recognizes similar peptides presented on healthy tissues.

Other names

PRAME-004HLA-A*02/PRAME(300-309)ALYVDSLFFL-HLA-A*02:01 complexPRAME ALY-HLA-A2

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex, leading to T-cell activation and directed cytotoxic lysis of the target cell.