{"entity":{"id":"cd137","kind":"target","name":"CD137 (4-1BB, TNFRSF9)","aka":["4-1BB","CD137","ILA","TNF receptor superfamily member 9"],"tldr":"4-1BB is a switch on activated T cells that makes them live longer and kill better. Rather than press it everywhere, new bispecific antibodies press it only on T cells that are already touching a tumour cell marked by PD-L1 or HER2.","summary":"TNFRSF9 (chromosome 1p36.23) encodes CD137 (4-1BB), the receptor for 4-1BB ligand (TNFSF9); its signal enhances CD8 T-cell survival, cytotoxicity and mitochondrial activity and so promotes immunity against viruses and tumours (UniProt Q07011). In OnCo it is the costimulatory arm of two tumour-anchored bispecifics: acasunlimab (PD-L1 x 4-1BB) in phase 3 for NSCLC, and cinrebafusp alfa (PRS-343), a HER2/4-1BB anticalin-antibody fusion protein that binds HER2 on tumour cells while engaging 4-1BB to costimulate T cells, in HER2-positive gastric cancer.","asOf":"2026-09-22","links":[{"label":"HGNC HGNC:11924","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11924"},{"label":"UniProt Q07011","url":"https://www.uniprot.org/uniprotkb/Q07011/entry"},{"label":"NCBI Gene 3604","url":"https://www.ncbi.nlm.nih.gov/gene/3604"}],"tags":["wave5-target"],"related":["pdl1","her2","cd28"],"cancers":["nsclc","gastric"],"sections":[],"technologies":["bispecific-antibody"],"targets":[],"drugs":["acasunlimab","cinrebafusp-alfa"],"companies":[],"institutions":[],"pathways":["cancer-immunity-cycle","pd1-checkpoint"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted."],"provenance":{"editedBy":"OnCo content wave 5 (HGNC REST, UniProt REST, corpus drug and pathway records)","editedOn":"2026-09-22"},"symbol":"TNFRSF9","role":["immune-checkpoint"],"sources":[],"specificity":"immune-microenvironment","distribution":"few-types","specificityNote":"Immune or microenvironment target: its medicines act on immune, stromal or bone cells rather than on the tumour cell (drug mechanisms in the corpus). HPA TNFRSF9: RNA tissue enhanced (lymphoid tissue 9 nTPM); blood lineage group enriched (granulocytes 9 nTPM, NK-cells 5 nTPM, T-cells 19 nTPM); no normal tissue stained high. Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Gastric & gastro-oesophageal junction cancer); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas TNFRSF9 tissue","url":"https://www.proteinatlas.org/ENSG00000049249-TNFRSF9/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt Q07011","url":"https://www.uniprot.org/uniprotkb/Q07011/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000049249 associations","url":"https://platform.opentargets.org/target/ENSG00000049249/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:11924","ensembl":"ENSG00000049249","uniprot":"Q07011","entrez":"3604","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Schwarz et al, Gene, 1993, \"A receptor induced by lymphocyte activation (ILA): a new member of the human nerve-growth-factor/tumor-necrosis-factor receptor family\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8262389/","biology":"Both corpus agents cluster 4-1BB only where the other arm has bound a tumour antigen (PD-L1 or HER2), so costimulation is confined to T cells in contact with the tumour rather than delivered systemically.","whereFound":["Activated CD8 T cells","NSCLC (acasunlimab) and HER2-positive gastric cancer (cinrebafusp alfa) trials"],"targetClass":"surface-antigen","prevalence":[]},"route":"/targets/cd137/","neighbours":{"target":[{"id":"cd27","kind":"target","name":"CD27","route":"/targets/cd27/"},{"id":"cd28","kind":"target","name":"CD28","route":"/targets/cd28/"},{"id":"tnfrsf18","kind":"target","name":"GITR (TNFRSF18)","route":"/targets/tnfrsf18/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"tnfrsf4","kind":"target","name":"OX40 (TNFRSF4)","route":"/targets/tnfrsf4/"},{"id":"pdl1","kind":"target","name":"PD-L1","route":"/targets/pdl1/"}],"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"drug":[{"id":"acasunlimab","kind":"drug","name":"Acasunlimab","route":"/drugs/acasunlimab/"},{"id":"cinrebafusp-alfa","kind":"drug","name":"Cinrebafusp alfa","route":"/drugs/cinrebafusp-alfa/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"cancer-immunity-cycle","kind":"pathway","name":"The cancer-immunity cycle","route":"/pathways/cancer-immunity-cycle/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}