HLA-A*02:01-restricted Preferentially Expressed Antigen in Melanoma (PRAME) complex (HLA-A*02:01/PRAME)

The HLA-A*02:01-restricted PRAME complex is a specific peptide-major histocompatibility complex (pMHC) found on the surface of various malignant cells. PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that is highly expressed in a wide range of cancers, including melanoma, sarcoma, and non-small cell lung cancer, while remaining largely absent from healthy adult tissues except for the testis [1, 2]. The specific epitope, typically the SLLQHLIGL peptide (PRAME 425-433), is processed and presented by the HLA-A*02:01 allele, making it a prime target for T-cell receptor (TCR) based therapies [3, 4]. Drugs like TSC-203 are engineered TCR-T cells designed to recognize this specific pMHC with high affinity and specificity, triggering a cytotoxic immune response against the tumor [1, 5]. This target is particularly valuable because HLA-A*02:01 is one of the most prevalent MHC alleles in the human population, and PRAME's restricted expression profile in healthy tissues minimizes the risk of widespread on-target, off-tumor toxicity [2, 6]. Clinical development of therapies targeting this complex focuses on solid tumors and hematologic malignancies where PRAME expression is a known driver of the oncogenic phenotype [1, 4].

Other names

PRAME-HLA-A*02:01 complexPRAME peptide-MHC complexHLA-A*02:01-SLLQHLIGLPRAME-A2Preferentially expressed antigen in melanoma presented by HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the specific PRAME peptide (SLLQHLIGL) presented by the HLA-A*02:01 molecule, leading to the activation of engineered T-cells and subsequent lysis of the target tumor cell.