Target intelligence / Profile preview

Melanoma-associated antigen 1 (MAGE-A1) peptide presented by HLA-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)
01

Overview

Melanoma-associated antigen 1 (MAGE-A1) is a member of the cancer-testis antigen family, which is typically expressed in various malignancies but restricted to the testis in healthy adults [6, 7]. The specific peptide epitope KVLEYVIKV (residues 278-286) is processed and presented on the cell surface by the HLA-A*02:01 molecule, forming a unique peptide-MHC complex [11, 12, 16]. This complex serves as a therapeutic target for T-cell receptor (TCR) engineered T-cell therapies, such as IMA202 and TK-8001, which are designed to recognize the target with high affinity and specificity [2, 4]. These therapies are currently being investigated in clinical trials for the treatment of MAGE-A1-positive solid tumors, including melanoma, hepatocellular carcinoma, and lung cancer [3, 5]. By leveraging the restricted expression of MAGE-A1, these drugs aim to induce potent anti-tumor immune responses while minimizing damage to normal tissues [9, 10]. However, challenges such as potential cross-reactivity with similar peptides in healthy tissues and the risk of cytokine release syndrome remain critical considerations in clinical development [4, 15].

Other names
MAGE-A1 peptide-MHC complexMAGE-A1(278-286) epitopeKVLEYVIKV/HLA-A*02:01MAGE-A1/HLA-A2
02

Mechanism of action

T-cell receptor (TCR) binding and subsequent T-cell mediated cytotoxicity

03

Biological functions

Antigen presentationImmune recognitionT-cell activationRegulation of ubiquitination
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Disease associations

CancerMelanomaHepatocellular carcinomaNon-small cell lung cancerSquamous cell carcinomaSarcoma
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Safety considerations

Off-target cross-reactivityCytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)
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Interacting drugs

IMA202

2 more in the full profile.

07

Biomarkers

MAGE-A1 expression (qPCR or IHC)HLA-A*02:01 genotype

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