Target intelligence / Profile preview

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

Target
MAGE-A1/HLA-A1
Molecular classification
Peptide-MHC complex, Cancer-Testis Antigen, Other
01

Overview

MAGE-A1 peptide presented by HLA-A1 is a specific peptide-major histocompatibility complex (pMHC) consisting of the EADPTGHSY nonamer peptide (residues 161-169) derived from the Melanoma-associated antigen 1 (MAGE-A1) protein and the Human Leukocyte Antigen A*01:01 molecule [1.1.1, 1.3.3]. MAGE-A1 is a member of the cancer-testis antigen (CTA) family, which is typically expressed only in male germ cells and various malignant tissues, making it an ideal target for cancer immunotherapy [1.5.1, 1.5.2]. The HLA-A1 restricted presentation of this peptide allows for the selective recognition of tumor cells by cytotoxic T lymphocytes (CTLs) or engineered T-cell receptor (TCR) therapies [1.3.5, 1.4.1]. This target is being actively explored in clinical and preclinical settings through therapeutic vaccines, TCR-engineered T-cell (TCR-T) therapies, and TCR-like antibodies [1.3.5, 1.4.1, 1.5.1]. Its high tumor specificity minimizes the risk of on-target off-tumor toxicity, although potential cross-reactivity with similar peptides in normal tissues, such as the Titin-derived peptide ESDPIVAQY, remains a critical safety consideration for high-affinity engineered receptors [1.2.1]. MAGE-A1 is frequently expressed in a variety of solid tumors, including melanoma, non-small cell lung cancer, and hepatocellular carcinoma, while HLA-A1 is a prevalent allele in Caucasian populations [1.3.5, 1.4.1].

Other names
MAGE-A1:HLA-A1 complexHLA-A1-restricted MAGE-A1 epitopeMAGE-A1(161-169)/HLA-A1EADPTGHSY/HLA-A*01:01MZ2-E antigenMAGE-1 peptide/HLA-A1
02

Mechanism of action

T-cell receptor (TCR) mediated recognition leading to T-cell activation and cytotoxic lysis of antigen-presenting tumor cells.

03

Biological functions

Immune responseAntigen presentationT-cell activation
04

Disease associations

Cancer
05

Safety considerations

Off-target toxicity due to cross-reactivity with similar self-peptides (e.g., Titin)On-target off-tumor toxicity (limited by CTA expression profile)HLA downregulation or loss of heterozygosity (LOH) in tumors
06

Interacting drugs

EADPTGHSY peptide vaccine

2 more in the full profile.

07

Biomarkers

MAGE-A1 expressionHLA-A*01:01 allele

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