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Preferentially expressed antigen in melanoma (PRAME) peptide (100-108) presented by Human leukocyte antigen A*02:01 (HLA-A*02:01) (PRAME100-108/HLA-A*02:01)

Target
PRAME100-108/HLA-A*02:01
Molecular classification
Peptide-MHC complex, Cancer-testis antigen (CTA), MHC class I-restricted antigen
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Overview

Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen (CTA) that acts as a repressor of retinoic acid receptor (RAR) signaling, thereby promoting tumor cell proliferation and inhibiting apoptosis [3]. The PRAME100-108 peptide, a nonamer with the sequence VLDGLDVLL, is a highly immunogenic epitope that is naturally processed and presented on the cell surface by the Human leukocyte antigen A*02:01 (HLA-A*02:01) molecule [4]. This specific peptide-MHC complex is a validated target for immunotherapy because PRAME is overexpressed in various cancers—including melanoma, uveal melanoma, and acute myeloid leukemia—while remaining largely absent in healthy adult tissues, except for the immune-privileged testis [3]. Current therapeutic approaches targeting this complex include TCR-engineered T-cell therapies (TCR-T), such as IMA203, and TCR-bispecific molecules like IMC-F106C, which redirect T cells to recognize and kill PRAME-presenting tumor cells [1, 2]. Clinical development of these agents requires patient screening for both the HLA-A*02:01 allele and sufficient PRAME expression levels to ensure efficacy and safety [1, 2].

Other names
PRAME VLDGLDVLL peptideHLA-A*02:01-restricted PRAME antigenPRAME-A2 complexVLDGLDVLL-HLA-A*02:01
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Mechanism of action

T-cell receptor (TCR) mediated recognition and lysis of tumor cells; Bispecific T-cell engagement (ImmTAC)

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Biological functions

Antigen presentationImmune recognitionT-cell activation
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Disease associations

MelanomaUveal melanomaAcute myeloid leukemiaNon-small cell lung cancerSynovial sarcomaOvarian cancer
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Safety considerations

Off-target cross-reactivity with similar peptidesOn-target off-tumor toxicity in testis or adrenal glandsCytokine release syndrome (CRS)
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Interacting drugs

IMA203

4 more in the full profile.

07

Biomarkers

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

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