CTLA-4
The first immune brake ever targeted for cancer; releasing it won a Nobel Prize and cures a fraction of melanomas. This dossier gathers the 3 products (3 approved), 15 trials, 3 pathways and 0 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
Competes with CD28 for B7 ligands during T-cell priming; also depletes regulatory T cells via Fc effector function.
- Activated and regulatory T cells
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →Products by modality and phase
Browse products →| Modality | Approved |
|---|---|
| Antibody 2 | |
| Bispecific antibody 1 |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| CheckMate 8HW NCT04008030 | 3 | Positive | MSI-H/dMMR metastatic colorectal cancer, all lines: nivolumab + ipilimumab vs nivolumab vs chemotherapy | First-line PFS 54.1 vs 5.9 months (HR 0.21); combination vs nivolumab PFS HR 0.62. | |
| CheckMate 9DW NCT04039607 | 3 | Positive | First-line unresectable HCC: nivolumab + ipilimumab vs lenvatinib or sorafenib | OS 23.7 vs 20.6 months, HR 0.79; ORR 36% vs 13%. | |
| COMPASSION-16 / AK104-303 NCT04982237 | 3 | Positive | Persistent, recurrent, or metastatic cervical cancer, first line (China): cadonilimab (PD-1×CTLA-4 bispecific) + platinum-paclitaxel ± bevacizumab vs placebo + chemotherapy ± bevacizumab | OS HR 0.64; PFS HR 0.62. | |
| NADINA NCT04949113 | 3 | Positive | Resectable macroscopic stage III melanoma: two cycles neoadjuvant ipilimumab + nivolumab then surgery (adjuvant only if incomplete response) vs surgery then 12 cycles adjuvant nivolumab | 12-month EFS 83.7% vs 57.2%; HR 0.32. | |
| COSMIC-313 NCT03937219 | 3 | Mixed | Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab | PFS HR 0.73; OS HR 1.02 (no benefit). | |
| HIMALAYA NCT03298451 | 3 | Positive | First-line unresectable HCC: STRIDE (single priming dose tremelimumab + durvalumab) vs sorafenib | OS HR 0.78; 5-year OS 19.6% vs 9.4%. | |
| CheckMate 648 NCT03143153 | 3 | Positive | First-line advanced oesophageal squamous cell carcinoma: nivolumab + chemotherapy, or nivolumab + ipilimumab (chemotherapy-free), vs chemotherapy | PD-L1 ≥1%: OS 15.4 vs 9.1 months (nivo + chemo, HR 0.54); 13.7 vs 9.1 months (nivo + ipi, HR 0.64). | |
| DREAMseq (ECOG-ACRIN EA6134) NCT02224781 | 3 | Positive | Untreated BRAF V600 metastatic melanoma: nivolumab + ipilimumab then dabrafenib + trametinib at progression, vs the reverse sequence | 2-year OS 71.8% vs 51.5%. | |
| CheckMate 743 NCT02899299 | 3 | Positive | Unresectable pleural mesothelioma, first line: nivolumab + ipilimumab vs platinum-pemetrexed | OS 18.1 vs 14.1 months, HR 0.74; 5-year OS 14% vs 6%. | |
| CASPIAN NCT03043872 | 3 | Positive | First-line extensive-stage SCLC: platinum-etoposide + durvalumab (± tremelimumab) vs platinum-etoposide | OS 13.0 vs 10.3 months, HR 0.73; 3-year OS 17.6% vs 5.8%. | |
| CheckMate 214 NCT02231749 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + ipilimumab vs sunitinib | 8-year OS HR 0.72 (ITT), 0.69 (intermediate/poor risk). | |
| CheckMate 067 NCT01844505 | 3 | Positive | Untreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab | 10-year OS 43% vs 37% vs 19%. | |
| KEYNOTE-006 NCT01866319 | 3 | Positive | Advanced melanoma, ≤1 prior systemic therapy: pembrolizumab (two schedules) vs ipilimumab | 10-year OS 34.0% vs 23.6%. | |
| NICHE-2 NCT03026140 | 2 | Positive | Locally advanced (mostly stage III) dMMR colon cancer: 4 weeks of neoadjuvant nivolumab + one dose ipilimumab, then surgery | pCR 68%, major pathologic response 95%; 3-year DFS 100%. |
Resistance routes that involve this target
Unaddressed routes →The resistance atlas has no route that names this target.
Pathways where it is a node
Pathway-to-drug matrix →- PD-1 / PD-L1 immune checkpoint & T-cell activationNode: CTLA-4 (stop) · 4 druggable nodes
How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.
Which nodes have drugs → - The cancer-immunity cycleNode: 3 Priming (CD28 / CTLA-4) · 3 druggable nodes
Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Which nodes have drugs → - Tumour microenvironment (TME)Node: Tregs (CTLA-4) · 5 druggable nodes
A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| MSI by PCR (Promega MSI Analysis System and equivalents) Promega and others · LDT | PCR | Instability at two or more of five markers (MSI-high); NGS panels report MSI from hundreds of loci |
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →No open questions recorded for this target yet. Suggest one.
Ideas and companies
Key papers and the live literature
Preprints →- CheckMate 067 at ten years: half of melanoma patients treated with nivolumab plus ipilimumab were alive a decade later · New England Journal of Medicine 2025
- CheckMate 067 at ten years: nivolumab plus ipilimumab produces long-term survival in half of patients with advanced melanoma · New England Journal of Medicine 2025
- NADINA: two doses of ipilimumab plus nivolumab before surgery beat a year of nivolumab after surgery in stage III melanoma · New England Journal of Medicine 2024
- NICHE-2: a month of nivolumab and ipilimumab before surgery clears mismatch-repair-deficient colon cancer in most patients · New England Journal of Medicine 2024
- NICHE-2: a single dose of ipilimumab and two of nivolumab before surgery clears dMMR colon cancer in most patients · New England Journal of Medicine 2024
- Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma · New England Journal of Medicine 2022
- ASCO 2021 guideline: how to recognise and manage the immune-related side effects of checkpoint inhibitors · Journal of Clinical Oncology 2021
- Hodi 2010: ipilimumab, the first checkpoint inhibitor, extends survival in metastatic melanoma · New England Journal of Medicine 2010
- Leach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours · Science 1996
Query for this target: (TITLE:"CTLA-4" OR ABSTRACT:"CTLA-4" OR TITLE:"CTLA4" OR ABSTRACT:"CTLA4") 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 CTLA-4, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/ctla4.json. Licence CC BY 4.0.