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TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.
TIGIT is an inhibitory receptor on T and NK cells that binds PVR (CD155) on tumour cells and competes with the activating receptor CD226, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. That expectation largely failed in phase 3: tiragolumab (SKYSCRAPER-01), domvanalimab and others did not add meaningful benefit to PD-1/PD-L1 blockade in NSCLC or SCLC, despite encouraging phase 2 signals. Because TIGIT sits on immune cells, patient selection relied on PD-L1 rather than a TIGIT-specific biomarker, and this remains a weakness. Fc-enabled versus Fc-silent antibody design, which changes whether regulatory T cells are depleted, is still debated, and some programmes continue. The newcomer's lesson: TIGIT is a cautionary tale about promising early data that did not survive large randomised trials.
In plain words · TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.
Backbone ribbon from PDB 8JEO. RCSB PDB 8JEO. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
TIGIT is an inhibitory receptor on T and natural killer cells that binds PVR (CD155) on tumour cells, so blocking it was expected to amplify PD-1 and PD-L1 inhibitors. Tiragolumab, domvanalimab and others then failed to add benefit in phase 3 lung cancer trials despite encouraging phase 2 signals, and the lack of a TIGIT-specific biomarker remains a weakness.
Binds PVR (CD155) on tumour cells; competes with the activating receptor CD226.
3 products aim at TIGIT: antibodies and 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 TIGIT: RNA tissue enriched (lymphoid tissue 36 nTPM); blood lineage lineage enriched (T-cells 196 nTPM); no normal tissue stained high. Distribution: 1 cancer family in the corpus carries a prevalence row, label threshold or catalogue link for it (Lung cancer (all types)); Open Targets associates it with 0 specific cancer types at or above 0.5. (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas TIGIT tissue; UniProt Q495A1; Open Targets ENSG00000181847 associations
First described 2004. Earliest sequence paper UniProt cites for the protein: Ota et al, Nat. Genet, 2004, "Complete sequencing and characterization of 21,243 full-length human cDNAs". Source.
Binds PVR (CD155) on tumour cells; competes with the activating receptor CD226.
RNA: tissue enriched (lymphoid tissue 36 nTPM), detected in some normal tissues. Blood: lineage enriched (T-cells 196 nTPM).
No normal tissue stained high.
No cancer sample stained medium or high.
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 |
|---|---|---|---|---|
| Non-small-cell lung cancer | n/a | Immune-cell target; PD-L1 used for selection | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
HB0036 is an experimental investigational agent whose form is not stated in the registry from Shanghai Huaota Biopharmaceutical in phase 2 trials for non-small-cell lung cancer, aimed at PD-L1 and TIGIT.
Rilvegostomig is an experimental bispecific antibody from AstraZeneca in phase 2 trials for non-small-cell lung cancer, aimed at PD-1 and TIGIT.
An immune-brake blocker that looked excellent in a phase 2 lung cancer trial and then failed every phase 3.
Query for this target: (TITLE:"TIGIT" OR ABSTRACT:"TIGIT") 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 TIGIT, not a curated reading list.
Shares TIM-3, T-cell exhaustion, Immune checkpoint, Checkpoint (two meanings) and the tag checkpoint.
Shares Checkpoint (two meanings), Cold tumours and the immunosuppressive microenvironment and the tags checkpoint, failed-so-far.
Shares T-cell exhaustion, Immune checkpoint, Checkpoint (two meanings), Cold tumours and the immunosuppressive microenvironment and the tag checkpoint.
Shares T-cell exhaustion, Immune checkpoint inhibitors and the tag failed-so-far.
Shares Compugen, TIM-3, Rilvegostomig, NK-cell recognition: missing self & stress ligands and the tag checkpoint.
Shares HB0036, Caution: TIGIT + PD-(L)1 blockade, Tiragolumab, T-cell exhaustion and the tag checkpoint.
Shares TIM-3, Checkpoint (two meanings), PD-1 / PD-L1 immune checkpoint & T-cell activation, Immune checkpoint inhibitors.
Shares TIGIT blockade, Tiragolumab, Small-cell lung cancer, Immune checkpoint inhibitors.