Preferentially expressed antigen in melanoma (PRAME) peptide 300–308 (SLLQHLIGL) presented by HLA-A*02:01 (PRAME300-308/HLA-A*02:01)

The PRAME300–308 peptide SLLQHLIGL presented by HLA-A*02:01 is a prominent peptide-major histocompatibility complex (pMHC) target in the field of cancer immunotherapy. PRAME (Preferentially expressed Antigen in Melanoma) is a cancer-testis antigen that is typically absent in most healthy adult tissues, except for the testis, but is highly overexpressed in a wide variety of solid and hematological malignancies [UniProt P78395, https://www.uniprot.org/uniprotkb/P78395/entry]. The specific 9-amino acid epitope SLLQHLIGL (residues 300-308) is processed intracellularly and presented on the cell surface by the HLA-A*02:01 allele, providing a highly specific 'molecular address' for T-cell recognition [PubMed, PMID: 11807012]. This target is currently being exploited by advanced therapeutic modalities, including TCR-engineered T-cell therapies like IMA203 and bispecific T-cell engagers like IMC-F106C [Immatics, https://immatics.com/pipeline/ima203/; Immunocore, https://www.immunocore.com/pipeline]. These therapies are designed to bypass natural immune tolerance by providing high-affinity receptors that specifically bind the SLLQHLIGL/HLA-A*02:01 complex, triggering a potent cytotoxic immune response against tumor cells. Clinical data have shown significant anti-tumor activity in patients with heavily pretreated PRAME-positive cancers, such as synovial sarcoma and melanoma [ClinicalTrials.gov, NCT03686124].

Other names

PRAME-004PRAME p300SLLQHLIGL-HLA-A2 complexPRAME300-308PRAME p300-308

T-cell receptor (TCR) mediated recognition of the specific peptide-MHC complex on the tumor cell surface, leading to T-cell activation, secretion of cytotoxic cytokines (e.g., IFN-gamma, TNF-alpha), and direct granzyme/perforin-mediated lysis of the target cell. Bispecific molecules (ImmTACs) bridge the pMHC complex to CD3 on polyclonal T-cells to induce a similar cytotoxic response.