Target intelligence / Profile preview

Melanoma-associated antigen 2 (MAGE-A2) (MAGE-A2)

Target
MAGE-A2
Molecular classification
Cancer-testis antigen, Melanoma-associated antigen family A
01

Overview

Melanoma-associated antigen 2 (MAGE-A2) is a member of the Type I Cancer-Testis Antigen (CTA) family, encoded by the MAGEA2 gene (UniProt P43356). Under physiological conditions, its expression is restricted to the immune-privileged germ cells of the testis, but it is frequently overexpressed in a wide array of human cancers, including melanoma and lung carcinoma (PubMed: 12149134). MAGE-A2 functions as an oncogene by interacting with and inhibiting the tumor suppressor p53, thereby promoting cell survival, proliferation, and resistance to apoptosis (PubMed: 15701743). In the context of immunotherapy, specific peptide sequences derived from MAGE-A2 are presented by Major Histocompatibility Complex (MHC) molecules on the surface of tumor cells. These MAGE-A2 peptide epitopes serve as targets for the development of therapeutic vaccines and T-cell receptor (TCR) engineered T-cell therapies designed to elicit a robust immune response against malignant cells while sparing normal tissues (PubMed: 9209195). However, therapeutic challenges include the potential for cross-reactivity with other MAGE family members and the risk of antigen escape through the downregulation of MHC molecules.

Other names
MAGE2MAGEA2Cancer/testis antigen 1.2CT1.2MAGE-A2 antigenMelanoma antigen family A 2
02

Mechanism of action

Presentation of peptide epitopes via MHC Class I molecules to activate CD8+ cytotoxic T-lymphocytes for targeted tumor cell lysis.

03

Biological functions

Inhibition of p53-mediated apoptosisCell cycle regulationPromotion of cell proliferationTranscriptional regulation
04

Disease associations

MelanomaNon-small cell lung cancerBreast cancerOvarian cancerHepatocellular carcinomaHead and neck squamous cell carcinoma
05

Safety considerations

On-target off-tumor toxicityCross-reactivity with other MAGE family proteinsImmune evasion via HLA downregulationPotential neurotoxicity due to MAGE family expression in the brain
06

Interacting drugs

MAGE-A2 peptide vaccine

2 more in the full profile.

07

Biomarkers

MAGE-A2 mRNA expressionMAGE-A2 protein expressionHLA-A*02:01 genotypeHLA-A*03 genotype

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