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Preferentially expressed Antigen in Melanoma-derived peptide SLLQHLIGL presented by Human Leukocyte Antigen A*02:01 (PRAME/HLA-A*02:01 (SLLQHLIGL))

Target
PRAME/HLA-A*02:01 (SLLQHLIGL)
Molecular classification
Peptide-MHC complex, Cancer-testis antigen (CTA) derivative, MHC Class I
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Overview

The Preferentially expressed Antigen in Melanoma (PRAME)-derived peptide SLLQHLIGL presented by Human Leukocyte Antigen A*02:01 (HLA-A*02:01) is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy (UniProt P78395). PRAME is a cancer-testis antigen that is highly expressed in various malignancies, such as melanoma, synovial sarcoma, and non-small cell lung cancer, but has restricted expression in healthy tissues, primarily the immune-privileged testis (PubMed PMID: 15901697). The specific nine-amino acid sequence SLLQHLIGL, corresponding to residues 425-433 of the PRAME protein, is processed and presented on the cell surface by the HLA-A*02:01 molecule, which is the most prevalent MHC Class I allele in Caucasian populations. This pMHC complex is recognized by specific T-cell receptors (TCRs), allowing for the development of targeted therapies that redirect the immune system to kill cancer cells. Current therapeutic approaches include TCR-engineered T-cell (TCR-T) therapies, such as the FDA-approved afamitresgene autoleucel (Tecelra), and soluble TCR-bispecific engagers like IMC-F106C (FDA, 2024; Immunocore, 2024). These agents bind the pMHC complex with high specificity, inducing T-cell activation and subsequent tumor cell lysis while minimizing damage to healthy tissues (Immatics N.V., 2024).

Other names
PRAME-004HLA-A2/PRAME(425-433)PRAME pMHC complexSLLQHLIGL/HLA-A*02:01PRAME-A2
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Mechanism of action

T-cell receptor (TCR) mediated recognition and redirection of T-cell cytotoxicity against cells presenting the specific PRAME peptide-MHC complex.

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Biological functions

Antigen presentationImmune recognitionT-cell activation
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Disease associations

MelanomaSynovial sarcomaNon-small cell lung cancerOvarian cancerUveal melanomaMultiple myeloma
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Safety considerations

Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)Off-target toxicity due to potential cross-reactivity with similar peptides in healthy tissues
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Interacting drugs

Afamitresgene autoleucel

3 more in the full profile.

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Biomarkers

HLA-A*02:01 genotypePRAME protein expression (IHC)PRAME mRNA expression (qPCR/RNA-seq)

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