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Melanoma-associated antigen 1 peptide presented by Human Leukocyte Antigen A*02:01 (MAGE-A1/HLA-A*02:01)

Target
MAGE-A1/HLA-A*02:01
Molecular classification
Peptide-MHC complex, Cancer-Testis Antigen (CTA) derivative, MHC Class I complex
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Overview

The MAGEA1-derived peptide presented by HLA-A*02:01 is a tumor-specific antigen complex that serves as a critical target for advanced cancer immunotherapies. MAGEA1 (Melanoma-associated antigen 1) is a member of the cancer-testis antigen family, which is typically expressed only in male germ cells and the placenta—tissues that do not express MHC Class I molecules. In various malignancies, MAGEA1 is aberrantly re-expressed, and its intracellular processing leads to the presentation of specific peptides, such as KVLEYVIKV, on the cell surface via the HLA-A*02:01 molecule [1][3]. Because HLA-A*02:01 is one of the most common MHC alleles in human populations, this complex is a highly attractive target for T-cell receptor (TCR) engineered therapies [4]. These therapies aim to exploit the high tumor specificity of MAGEA1 to induce potent cytotoxic T-lymphocyte responses while minimizing damage to normal somatic tissues [2]. Current clinical development focuses on optimizing TCR affinity to ensure robust anti-tumor activity and safety against potential cross-reactive epitopes.

Other names
MAGE-A1/HLA-A2 complexMAGE-A1 peptide-MHC complexMAGE-A1 pMHCMelanoma antigen family A 1 peptide-HLA-A*02:01 complex
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Mechanism of action

Therapeutic agents, such as TCR-engineered T-cells, specifically bind to the MAGE-A1 peptide presented within the groove of the HLA-A*02:01 molecule on the surface of tumor cells. This binding event triggers T-cell activation, leading to the release of perforins and granzymes, which induce apoptosis and selective lysis of the target cancer cell.

03

Biological functions

Antigen presentationT-cell activationImmune recognitionInduction of cytotoxic T-lymphocyte response
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Disease associations

MelanomaNon-small cell lung cancerHepatocellular carcinomaMultiple myelomaHead and neck squamous cell carcinoma
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Safety considerations

Off-target cross-reactivity with similar self-peptides in healthy tissuesCytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)On-target off-tumor toxicity if MAGEA1 is expressed at low levels in vital organs
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Interacting drugs

TCR-engineered T-cells (TCR-T)

3 more in the full profile.

07

Biomarkers

MAGEA1 mRNA expression (RT-qPCR)MAGEA1 protein expression (Immunohistochemistry)HLA-A*02:01 allele positivityInterferon-gamma release (ELISPOT)

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