Target intelligence / Profile preview

Melanoma-associated antigen 1 presented on HLA-A*02:01 (MAGE-A1/HLA-A*02:01)

Target
MAGE-A1/HLA-A*02:01
Molecular classification
Other (peptide–MHC I complex), Tumor antigen (peptide), Major histocompatibility complex class I ligand
01

Overview

The melanoma-associated antigen 1 presented on HLA-A*02:01 is a defined antigenic peptide from the MAGE-A1 gene product, complexed with the HLA-A*02:01 MHC class I molecule on the surface of tumor cells, especially melanomas. This complex serves as a target for T cell-based immunotherapies, including adoptive T cell transfer and peptide vaccines, due to its restricted expression in tumor cells (not normal somatic tissues except testis) and its ability to be recognized by cytotoxic T lymphocytes. The interaction enables immune-mediated destruction of tumor cells. HLA-A*02:01 is one of the most common class I MHC alleles in human populations, making this target broadly relevant for immunotherapy development[3][4][1]. MAGE-A1 is the full gene name for Melanoma-associated antigen 1; peptides derived from this are presented on HLA-A*02:01 on melanoma (and some other tumor) cells and recognized by cytotoxic T cells[4][3]. This complex is the molecular basis for some personalized and off-the-shelf cancer immunotherapies and cancer vaccines[3][4]. Primary utility is in cancer immunotherapy, biomarker development, and research into tumor immune recognition[4][3][1].

Other names
MAGE-A1 presented by HLA-A*02:01MAGE1/HLA-A*02:01 complexMelanoma antigen gene-A1/HLA-A2 complexMZ2-E/HLA-A*02:01 (historical, for antigen recognized by CTL)
02

Mechanism of action

Stimulation of cytotoxic T lymphocytes (CTLs) that recognize the peptide-MHC complex leading to tumor cell lysis[4][3] CTL-based killing of melanoma cells presenting MAGE-A1 on HLA-A*02:01[3] Immune checkpoint inhibition enables CTLs to more effectively target this complex[4]

03

Biological functions

Immune responseAntigen presentationTumor immune recognition
04

Disease associations

Cancer (particularly melanoma)Tumor immunology
05

Safety considerations

Risk of autoimmunity if normal cells express MAGE-A1 ectopically[4]Tumor immune escape through antigen loss or HLA downregulationUnintended cross-reactivity of engineered TCRsAdverse immune-related events from immune checkpoint blockade
06

Interacting drugs

Ipilimumab (indirectly, via enhanced T cell response)

4 more in the full profile.

07

Biomarkers

Presence of MAGE-A1 mRNA/protein expression (as indication for immunotherapy targeting)HLA-A*02:01 positivity (required for T cell-based therapies to recognize this complex)

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