Loading
A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it.
MAGE-A4 is a cancer-testis antigen: an intracellular protein normally confined to testis that some tumours switch back on. It is presented on the cell surface only as peptide fragments in HLA, chiefly HLA-A*02, so it cannot be reached by antibodies or conventional CAR-T and is targetable only through T-cell receptor based approaches. Afamitresgene autoleucel (Tecelra), the first TCR-T therapy approved for a solid tumour (synovial sarcoma, 2024), recognises a MAGE-A4 peptide. Expression is seen in roughly 60 to 80 percent of synovial sarcomas and in myxoid liposarcoma, with subsets of squamous lung, ovarian and gastric cancers, but patients must also carry HLA-A*02, which about 40 to 45 percent of the population do. Durability of responses and extension beyond sarcoma are the open questions. Think of it as a hidden protein that engineered T cells can be taught to spot in fragments.
In plain words · A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it.
A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it.
Intracellular; presented as peptide-HLA complex.
1 product aims at MAGE-A4: cell therapies. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
Tumour-associated overexpression: 1 cell-killing or cell-finding medicine (Afamitresgene autoleucel) aim at the antigen, which HPA finds stained high in 1 normal tissue; the medicine relies on the tumour carrying more of it than the normal tissue it shares it with. HPA MAGEA4: RNA tissue enriched (testis 21 nTPM); high antibody staining in 1 normal tissue; highest cancer staining testis cancer (4 of 12 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Sarcomas (soft tissue, bone, GIST), Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 5 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas MAGEA4 tissue; Human Protein Atlas MAGEA4 pathology; Open Targets ENSG00000147381 associations
First described 1994. Earliest sequence paper UniProt cites for the protein: De Plaen et al, Immunogenetics, 1994, "Structure, chromosomal localization, and expression of 12 genes of the MAGE family". Source.
Intracellular; presented as peptide-HLA complex.
RNA: tissue enriched (testis 21 nTPM), detected in some normal tissues.
RNA cancer enhanced: Lung Squamous Cell Carcinoma 95 pTPM.
Medium only: breast cancer, colorectal cancer, lung cancer, melanoma.
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Sarcomas | 60-80% | Synovial sarcoma, IHC/RNA | HLA-A*02 needed for TCR-T; ~40-45% of population | Wikipedia |
| Non-small-cell lung cancer | 20-30% | Squamous enriched | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Afamitresgene autoleucel was the first engineered T-cell receptor therapy approved for a solid tumour, synovial sarcoma.
Query for this target: (TITLE:"MAGE-A4" OR ABSTRACT:"MAGE-A4" OR TITLE:"MAGEA4" OR ABSTRACT:"MAGEA4") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MAGE-A4, not a curated reading list.
Shares HLA-A, TCR-T cell therapy, Antigen presentation & immune editing, Melanoma and the tag tcr-target.
Shares HLA-A, TCR-T cell therapy, Antigen presentation & immune editing, Sarcomas (soft tissue, bone, GIST) and the tag tcr-target.
Shares Extending sarcoma TCR-T beyond HLA-A*02, SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma, HLA-A, TCR-T cell therapy.
Shares SS18::SSX fusion (synovial sarcoma), Afamitresgene autoleucel, TCR-T cell therapy, Antigen presentation & immune editing.
Shares Afamitresgene autoleucel, SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma, Sarcomas (soft tissue, bone, GIST).
Shares Afamitresgene autoleucel, TCR-T cell therapy, Sarcomas (soft tissue, bone, GIST).
Shares Afamitresgene autoleucel, HLA-A, Melanoma.