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

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

Overview

The HLA-A*02:01-restricted PRAME-derived peptide complex is a prominent target in the field of cancer immunotherapy, specifically for T-cell receptor (TCR)-based interventions [1]. PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer-testis antigen that is highly expressed in a wide range of solid and hematological malignancies but has very limited expression in normal adult tissues, primarily the testis and ovaries [2]. The specific peptide sequence, most commonly the SLLMWITQC epitope, is processed and presented on the cell surface by the HLA-A*02:01 allele, which is one of the most prevalent MHC class I molecules in human populations [3]. This peptide-MHC (pMHC) complex serves as a "flag" for the immune system, allowing engineered TCR-T cells or bispecific T-cell engagers to identify and destroy malignant cells [4]. Therapeutic strategies targeting this complex, such as ImmTACs (Immune mobilizing monoclonal TCRs against cancer) and TCR-engineered T-cells, are currently in clinical trials for various indications including melanoma and lung cancer [5]. The high specificity of the PRAME-A2 complex makes it an attractive candidate for reducing off-target effects while maximizing anti-tumor efficacy [6].

Other names
PRAME SLLMWITQC peptideHLA-A2/PRAME complexPRAME-A2PRAME-derived peptide-MHC complex
02

Mechanism of action

T-cell receptor (TCR) mediated recognition and subsequent T-cell directed lysis of tumor cells.

03

Biological functions

Antigen presentationImmune recognitionT-cell activation
04

Disease associations

MelanomaNon-small cell lung cancerUveal melanomaSynovial sarcomaAcute myeloid leukemia
05

Safety considerations

Cytokine release syndrome (CRS)Off-target toxicityOn-target off-tumor toxicity
06

Interacting drugs

IMC-F106C

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypePRAME mRNA expressionPRAME protein expression (IHC)

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