Human leukocyte antigen A*02:01-presented preferentially expressed antigen in melanoma (PRAME) peptide (SLLMWITQC) (HLA-A2/PRAME)

The HLA-A*02:01-presented PRAME peptide is a specific peptide-major histocompatibility complex (pMHC) target located on the surface of various malignant cells [PubMed: 28603134]. PRAME (Preferentially expressed Antigen in Melanoma) is a member of the cancer-testis antigen family, which is characterized by high expression in tumors and restricted expression in normal tissues, primarily the testis, making it an ideal candidate for immunotherapy [PubMed: 15958671]. The specific peptide, typically the nonamer SLLMWITQC (PRAME 300-308), is processed from the intracellular PRAME protein and presented by the HLA-A*02:01 allele [PubMed: 15958671]. This complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, triggering an immune response against the tumor [Immunocore, 2022]. Current therapeutic developments targeting this pMHC include TCR-engineered T-cell therapies (TCR-T) and bispecific TCR molecules, such as ImmTACs, which bridge T-cells to tumor cells [Adaptimmune, 2023]. These therapies aim to exploit the high tumor specificity of PRAME to treat cancers like uveal melanoma, cutaneous melanoma, and various solid tumors while minimizing off-target effects [PubMed: 36121340]. Because the target is an intracellular protein fragment presented on the surface, it allows for the targeting of proteins that are not accessible by traditional antibody-based therapies [PubMed: 28603134]. Patient selection for these therapies requires both the presence of the HLA-A*02:01 allele and confirmed expression of the PRAME antigen in the tumor tissue [Immunocore, 2022].

Other names

PRAME-A2 complexHLA-A*02:01/PRAME(SLLMWITQC)PRAME peptide-MHC complexPRAME300-308/HLA-A*02:01Melanoma antigen preferentially expressed in tumorsOIP4MAPE

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