{"entity":{"id":"tim3","kind":"target","name":"TIM-3","aka":[],"tldr":"An immune checkpoint on exhausted T cells and on leukaemic stem cells; antibodies against it failed in lung cancer and MDS after strong preclinical promise.","summary":"TIM-3 (HAVCR2) is co-expressed with PD-1 on the most exhausted T cells and on leukaemic stem cells (not normal HSCs), and its ligands include galectin-9, CEACAM1, HMGB1 and phosphatidylserine. Sabatolimab plus azacitidine failed in higher-risk MDS (STIMULUS-MDS2, 2023); cobolimab plus dostarlimab in NSCLC (COSTAR Lung) missed its primary endpoint (2024); other anti-TIM-3 antibodies (LY3321367, TSR-022, MBG453) were discontinued or de-prioritised. Remains a rational target in PD-1-refractory disease and for leukaemic stem-cell targeting (CAR-T).","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/HAVCR2","links":[{"label":"STIMULUS-MDS2 (Lancet Haematol 2024)","url":"https://doi.org/10.1016/S2352-3026(23)00333-2"}],"tags":["gap-fill","negative-trials"],"related":["lag3","tigit","pd1"],"cancers":["mds","aml","nsclc"],"sections":[],"technologies":["checkpoint-inhibitor","tim3-blockade"],"targets":[],"drugs":["azd7789","lb1410"],"companies":[],"institutions":[],"pathways":["pd1-checkpoint","t-cell-exhaustion"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-zeidan-lancet-haematol"],"journals":[],"dependsOn":[],"notes":["Prevalence is not well characterised as a positivity rate: TIM-3 marks leukaemic stem cells in most non-APL AML (Kikushige 2010, doi:10.1016/j.stem.2010.11.014; Jan 2011, doi:10.1073/pnas.1100551108) and exhausted T cells in the microenvironment of MDS and NSCLC, but no standard cutoff or per-cancer percentage has been published."],"symbol":"HAVCR2","role":["immune-checkpoint"],"sources":[],"specificity":"immune-microenvironment","distribution":"few-types","specificityNote":"Immune or microenvironment target: the record's class is immune checkpoint. HPA HAVCR2: RNA low tissue specificity; blood lineage group enriched (dendritic cells 119 nTPM, monocytes 63 nTPM, NK-cells 76 nTPM); high antibody staining in 1 normal tissue. Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Myeloid neoplasms, Leukaemia, Lung cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (subcutaneous panniculitis-like T-cell lymphoma). (Rule 1 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas HAVCR2 tissue","url":"https://www.proteinatlas.org/ENSG00000135077-HAVCR2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"UniProt Q8TDQ0","url":"https://www.uniprot.org/uniprotkb/Q8TDQ0/entry","note":"involvement in disease"},{"label":"Open Targets ENSG00000135077 associations","url":"https://platform.opentargets.org/target/ENSG00000135077/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:18437","ensembl":"ENSG00000135077","uniprot":"Q8TDQ0","entrez":"84868","firstDescribed":2000,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Zhang et al, 2000, \"Novel human hepatitis A virus cellular receptor\".","firstDescribedSource":"https://www.uniprot.org/uniprotkb/Q8TDQ0/entry","biology":"Type I transmembrane receptor of the TIM family; ligand binding recruits BAT3 release and inhibits TCR signalling; on myeloid cells it regulates innate responses. Marks terminal exhaustion together with PD-1, LAG-3 and TIGIT.","whereFound":["Exhausted CD8 T cells in most solid tumours","Leukaemic stem cells in AML and MDS","Tumour-associated macrophages"],"targetClass":"checkpoint","prevalence":[{"cancerId":"metastatic-cancer","pct":"immune","measure":"Immune-cell target (TIM-3 checkpoint on exhausted T cells and myeloid cells): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers."}]},"route":"/targets/tim3/","neighbours":{"target":[{"id":"lgals9","kind":"target","name":"Galectin-9 (LGALS9)","route":"/targets/lgals9/"},{"id":"lag3","kind":"target","name":"LAG-3","route":"/targets/lag3/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"},{"id":"tigit","kind":"target","name":"TIGIT","route":"/targets/tigit/"},{"id":"vista","kind":"target","name":"VISTA","route":"/targets/vista/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"mds-higher-risk","kind":"cancer","name":"Higher-risk myelodysplastic syndromes","route":"/cancers/mds-higher-risk/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"},{"id":"tim3-blockade","kind":"technology","name":"TIM-3 blockade","route":"/technologies/tim3-blockade/"}],"drug":[{"id":"azd7789","kind":"drug","name":"AZD7789","route":"/drugs/azd7789/"},{"id":"lb1410","kind":"drug","name":"LB1410","route":"/drugs/lb1410/"}],"pathway":[{"id":"pd1-checkpoint","kind":"pathway","name":"PD-1 / PD-L1 immune checkpoint & T-cell activation","route":"/pathways/pd1-checkpoint/"},{"id":"t-cell-exhaustion","kind":"pathway","name":"T-cell exhaustion","route":"/pathways/t-cell-exhaustion/"}],"paper":[{"id":"paper-pardoll-immune-checkpoint-blockade-nrc-2012","kind":"paper","name":"Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy","route":"/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/"},{"id":"paper-zeidan-lancet-haematol","kind":"paper","name":"Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial","route":"/key-papers/paper-zeidan-lancet-haematol/"}],"term":[{"id":"checkpoint","kind":"term","name":"Checkpoint (two meanings)","route":"/terms/checkpoint/"}]}}