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Melanoma-associated antigen 10 (MAGE-A10) peptide GLYDGMEHL (254-262) presented by HLA-A*02:01 (MAGE-A10/HLA-A*02:01)

Target
MAGE-A10/HLA-A*02:01
Molecular classification
Peptide-MHC complex, Cancer-testis antigen (CTA)
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Overview

The MAGE-A10 peptide GLYDGMEHL (residues 254-262) presented by the Human Leukocyte Antigen (HLA)-A*02:01 is a specific peptide-MHC complex that serves as a target for cancer immunotherapy. MAGE-A10 belongs to the cancer-testis antigen (CTA) family, which is characterized by high expression in various malignant tumors but restricted expression in normal adult tissues, primarily the immune-privileged testes and placenta. This expression pattern makes the GLYDGMEHL-HLA-A*02:01 complex an ideal target for T-cell receptor (TCR) engineered T-cell therapies, as it allows for the selective destruction of cancer cells while sparing healthy somatic tissue. In clinical oncology, this target is particularly relevant for patients with HLA-A*02:01-positive tumors that overexpress MAGE-A10, such as melanoma and non-small cell lung cancer. Therapeutic strategies, such as Adaptimmune's ADP-A2M10, utilize affinity-enhanced TCRs to recognize this specific complex and trigger a potent cytotoxic immune response against the tumor. However, development requires rigorous screening to avoid cross-reactivity with similar peptides found in vital organs, which could lead to severe adverse events.

Other names
MAGEA10 peptide GLYDGMEHLGLYDGMEHL-HLA-A*02:01 complexCancer/testis antigen 1.10MAGE-10
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Mechanism of action

T-cell receptor (TCR) mediated cytotoxicity

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Biological functions

Antigen presentationImmune recognitionT-cell activation
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Disease associations

MelanomaNon-small cell lung cancerUrothelial carcinomaHead and neck squamous cell carcinoma
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Safety considerations

Off-target toxicity due to cross-reactivity with similar peptides in healthy tissuesCytokine release syndrome (CRS)NeurotoxicityOn-target, off-tumor toxicity
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Interacting drugs

ADP-A2M10
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Biomarkers

HLA-A*02:01 genotypeMAGE-A10 mRNA expressionMAGE-A10 protein expression (IHC)

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