# TIM-3

Source: https://onco.cc/targets/tim3/  
OnCo record `tim3` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Target
- Last checked: 2026-09-08
- Tags: gap-fill; negative-trials
- Symbol: HAVCR2
- Class: checkpoint
- 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.
- Where found: Exhausted CD8 T cells in most solid tumours; Leukaemic stem cells in AML and MDS; Tumour-associated macrophages

## 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/HAVCR2
- STIMULUS-MDS2 (Lancet Haematol 2024): https://doi.org/10.1016/S2352-3026(23)00333-2

## Connected records

- targets: [Galectin-9 (LGALS9)](https://onco.cc/targets/lgals9/), [LAG-3](https://onco.cc/targets/lag3/), [PD-1](https://onco.cc/targets/pd1/), [TIGIT](https://onco.cc/targets/tigit/), [VISTA](https://onco.cc/targets/vista/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Higher-risk myelodysplastic syndromes](https://onco.cc/cancers/mds-higher-risk/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [TIM-3 blockade](https://onco.cc/technologies/tim3-blockade/)
- drugs: [AZD7789](https://onco.cc/drugs/azd7789/), [LB1410](https://onco.cc/drugs/lb1410/)
- pathways: [PD-1 / PD-L1 immune checkpoint & T-cell activation](https://onco.cc/pathways/pd1-checkpoint/), [T-cell exhaustion](https://onco.cc/pathways/t-cell-exhaustion/)
- key papers: [Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy](https://onco.cc/key-papers/paper-pardoll-immune-checkpoint-blockade-nrc-2012/), [Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial](https://onco.cc/key-papers/paper-zeidan-lancet-haematol/)
- terms: [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/)

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