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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.
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).
In plain words · 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.
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.
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.
2 products aim at TIM-3: bispecific antibodies. Checkpoint drugs are antibodies that cover one side of an immune ‘stand down’ handshake so T cells stay active.
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.)
Sources: Human Protein Atlas HAVCR2 tissue; UniProt Q8TDQ0; Open Targets ENSG00000135077 associations
First described 2000. Earliest sequence paper UniProt cites for the protein: Zhang et al, 2000, "Novel human hepatitis A virus cellular receptor". Source.
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.
RNA: low tissue specificity, detected in all normal tissues. Blood: group enriched (dendritic cells 119 nTPM, monocytes 63 nTPM, NK-cells 76 nTPM).
Medium: Colon, Duodenum, Lymph node, Rectum, Tonsil.
RNA cancer enhanced: Kidney Renal Clear Cell Carcinoma 62 pTPM.
No cancer stained high; medium in renal cancer.
HPA HAVCR2 tissue · HPA HAVCR2 pathology · HPA protein class: CD markers
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 |
|---|---|---|---|---|
| Metastatic cancer | immune% | 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. |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AZD7789 is an experimental bispecific antibody from AstraZeneca in phase 2 trials for non-small-cell lung cancer and gastric & gastro-oesophageal junction cancer, aimed at PD-1 and TIM-3.
LB1410 is an experimental bispecific antibody from L & L Bio, Ningbo, China in phase 2 trials, aimed at PD-1 and TIM-3.
One target page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
This is the most cited map of the immunotherapy revolution and a good first read before the trials. Its predictions largely held: PD-1 pathway antibodies became the most widely used cancer drugs, PD-L1 testing entered practice, and LAG-3 blockade was approved in melanoma a decade later.
Query for this target: (TITLE:"TIM-3" OR ABSTRACT:"TIM-3" OR TITLE:"HAVCR2" OR ABSTRACT:"HAVCR2") 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 TIM-3, not a curated reading list.
Shares Galectin-9 (LGALS9), TIM-3 blockade, Non-small-cell lung cancer.
Shares TIGIT, Checkpoint (two meanings), Immune checkpoint inhibitors, Non-small-cell lung cancer.
Shares Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1, Immune checkpoint inhibitors.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1, Immune checkpoint inhibitors.
Shares LAG-3, T-cell exhaustion, PD-1 / PD-L1 immune checkpoint & T-cell activation, PD-1.
Shares Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, TIGIT, LAG-3, Checkpoint (two meanings).