{"entity":{"id":"mage-a4","kind":"target","name":"MAGE-A4","aka":[],"tldr":"A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it.","summary":"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.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/MAGEA4","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/MAGEA4"}],"tags":["tcr-target"],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":[],"targets":[],"drugs":["afamitresgene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"MAGEA4","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas MAGEA4 tissue","url":"https://www.proteinatlas.org/ENSG00000147381-MAGEA4/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas MAGEA4 pathology","url":"https://www.proteinatlas.org/ENSG00000147381-MAGEA4/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000147381 associations","url":"https://platform.opentargets.org/target/ENSG00000147381/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:6802","ensembl":"ENSG00000147381","uniprot":"P43358","entrez":"4103","firstDescribed":1994,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7927540/","biology":"Intracellular; presented as peptide-HLA complex.","whereFound":["Synovial sarcoma","Myxoid liposarcoma","NSCLC, ovarian, gastric (subsets)"],"targetClass":"other","prevalence":[{"cancerId":"sarcoma","pct":"60-80","measure":"Synovial sarcoma, IHC/RNA","source":"https://en.wikipedia.org/wiki/MAGEA4","note":"HLA-A*02 needed for TCR-T; ~40-45% of population"},{"cancerId":"nsclc","pct":"20-30","measure":"Squamous enriched","source":"https://en.wikipedia.org/wiki/MAGEA4"}]},"route":"/targets/mage-a4/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"drug":[{"id":"afamitresgene-autoleucel","kind":"drug","name":"Afamitresgene autoleucel","route":"/drugs/afamitresgene-autoleucel/"}],"idea":[{"id":"idea-tcr-t-beyond-hla-a2","kind":"idea","name":"Extending sarcoma TCR-T beyond HLA-A*02","route":"/ideas/idea-tcr-t-beyond-hla-a2/"}],"technology":[{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"company":[{"id":"tscan","kind":"company","name":"TScan Therapeutics","route":"/companies/tscan/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"}],"person":[{"id":"sandra-dangelo","kind":"person","name":"Sandra P. D'Angelo","route":"/people/sandra-dangelo/"}],"pathway":[{"id":"antigen-presentation-immunoediting","kind":"pathway","name":"Antigen presentation & immune editing","route":"/pathways/antigen-presentation-immunoediting/"}],"paper":[{"id":"paper-spearhead-1-lancet-2024","kind":"paper","name":"SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma","route":"/key-papers/paper-spearhead-1-lancet-2024/"}],"term":[{"id":"ss18-ssx-fusion","kind":"term","name":"SS18::SSX fusion (synovial sarcoma)","route":"/terms/ss18-ssx-fusion/"}],"target":[{"id":"hla-a","kind":"target","name":"HLA-A","route":"/targets/hla-a/"}]}}