{"title":"OnCo checkpoint families: Immune checkpoints","page":"https://onco.cc/checkpoints/immune/","licence":"https://creativecommons.org/licenses/by-nc/4.0/","root":"immune","classes":[{"id":"inhibitory-receptor","name":"Inhibitory receptors on T and NK cells","tone":"inhibitory","plain":"Brakes carried by the immune cell itself. When the receptor meets its ligand on a tumour cell or an antigen-presenting cell, the T cell or NK cell stands down. Antibodies that block the receptor release the brake.","evidence":{"text":"PD-1 and CTLA-4 antibodies shaped treatment, most patients still show primary or adaptive resistance, and LAG-3, TIM-3, TIGIT and VISTA are the next checkpoints characterised.","source":{"label":"Qin et al. 2019, Mol Cancer: novel immune checkpoint targets beyond PD-1 and CTLA-4","url":"https://europepmc.org/article/MED/31690319"}},"members":[{"id":"pd1","label":"PD-1","symbol":"PDCD1","hgnc":"HGNC:8760","side":"immune-cell","target":"https://onco.cc/targets/pd1/","page":"https://onco.cc/checkpoints/immune/#pd1","expressedOn":{"text":"Antigen-activated T cells; delivers inhibitory signals on binding PD-L1 or PD-L2.","source":{"label":"UniProt Q15116","url":"https://www.uniprot.org/uniprotkb/Q15116/entry"}},"partners":["pdl1","pdcd1lg2"],"bestStatus":{"status":"approved","drug":"pembrolizumab"},"drugs":[{"id":"pembrolizumab","name":"Pembrolizumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/pembrolizumab/"},{"id":"nivolumab","name":"Nivolumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/nivolumab/"},{"id":"cemiplimab","name":"Cemiplimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/cemiplimab/"},{"id":"dostarlimab","name":"Dostarlimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/dostarlimab/"},{"id":"toripalimab","name":"Toripalimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/toripalimab/"},{"id":"tislelizumab","name":"Tislelizumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/tislelizumab/"},{"id":"retifanlimab","name":"Retifanlimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/retifanlimab/"},{"id":"sintilimab","name":"Sintilimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/sintilimab/"},{"id":"camrelizumab","name":"Camrelizumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/camrelizumab/"},{"id":"serplulimab","name":"Serplulimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/serplulimab/"},{"id":"penpulimab","name":"Penpulimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/penpulimab/"},{"id":"zimberelimab","name":"Zimberelimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/zimberelimab/"},{"id":"relatlimab-nivolumab","name":"Relatlimab + nivolumab","drugClass":"antibody","status":"approved","note":"fixed-dose combination with the LAG-3 antibody relatlimab","page":"https://onco.cc/drugs/relatlimab-nivolumab/"},{"id":"cadonilimab","name":"Cadonilimab","drugClass":"bispecific","status":"approved","note":"PD-1 x CTLA-4","page":"https://onco.cc/drugs/cadonilimab/"},{"id":"ivonescimab","name":"Ivonescimab","drugClass":"bispecific","status":"approved","note":"PD-1 x VEGF","page":"https://onco.cc/drugs/ivonescimab/"},{"id":"rilvegostomig","name":"Rilvegostomig","drugClass":"bispecific","status":"phase-2","note":"PD-1 x TIGIT","page":"https://onco.cc/drugs/rilvegostomig/"},{"id":"ai-081","name":"AI-081","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/ai-081/"},{"id":"azd7789","name":"AZD7789","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/azd7789/"},{"id":"bcd-217","name":"BCD-217","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/bcd-217/"},{"id":"camrelizumab-rivoceranib","name":"Camrelizumab + rivoceranib","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/camrelizumab-rivoceranib/"},{"id":"gc101-til","name":"GC101 TIL","drugClass":"cell-therapy","status":"phase-2","page":"https://onco.cc/drugs/gc101-til/"},{"id":"ibi363","name":"IBI363","drugClass":"fusion-protein","status":"phase-2","page":"https://onco.cc/drugs/ibi363/"},{"id":"lb1410","name":"LB1410","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/lb1410/"},{"id":"lorigerlimab","name":"Lorigerlimab","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/lorigerlimab/"},{"id":"pucotenlimab","name":"Pucotenlimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/pucotenlimab/"},{"id":"sasanlimab","name":"Sasanlimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/sasanlimab/"},{"id":"ssgj-705","name":"SSGJ-705","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/ssgj-705/"},{"id":"ssgj-706","name":"SSGJ-706","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/ssgj-706/"},{"id":"t3011","name":"T3011","drugClass":"small-molecule","status":"phase-2","page":"https://onco.cc/drugs/t3011/"},{"id":"tak-928","name":"TAK-928","drugClass":"bispecific","status":"phase-3","page":"https://onco.cc/drugs/tak-928/"},{"id":"tqb2450","name":"TQB2450","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/tqb2450/"}],"approvals":[{"drug":"pembrolizumab","region":"US","year":2014,"indication":"Melanoma (first of >40 indications)"},{"drug":"nivolumab","region":"US","year":2014,"indication":"Melanoma"},{"drug":"pembrolizumab","region":"US","year":2017,"indication":"MSI-H/dMMR solid tumours (tumour-agnostic)"},{"drug":"toripalimab","region":"China","year":2018,"indication":"Melanoma (first of many indications)"},{"drug":"sintilimab","region":"China","year":2018,"indication":"Relapsed or refractory classical Hodgkin lymphoma after two or more lines"},{"drug":"cemiplimab","region":"US","year":2018,"indication":"Advanced cutaneous squamous cell carcinoma"},{"drug":"tislelizumab","region":"China","year":2019,"indication":"Classical Hodgkin lymphoma (first); subsequently urothelial, NSCLC, HCC, ESCC, gastric, nasopharyngeal"},{"drug":"camrelizumab","region":"China","year":2019,"indication":"Classical Hodgkin lymphoma; subsequently HCC, NSCLC, ESCC (second line 2020, first line with chemotherapy 2021), nasopharyngeal"},{"drug":"pembrolizumab","region":"US","year":2020,"indication":"Metastatic TNBC, PD-L1 CPS ≥10, with chemotherapy"},{"drug":"sintilimab","region":"China","year":2021,"indication":"First-line non-squamous NSCLC with pemetrexed and platinum (ORIENT-11); first-line squamous NSCLC with gemcitabine and platinum (ORIENT-12); first-line unresectable hepatocellular carcinoma with IBI305 (ORIENT-32)"},{"drug":"penpulimab","region":"CN","year":2021,"indication":"Relapsed/refractory classical Hodgkin lymphoma; later NPC, NSCLC"},{"drug":"zimberelimab","region":"CN","year":2021,"indication":"Relapsed or refractory classical Hodgkin lymphoma after two or more lines of therapy"},{"drug":"pembrolizumab","region":"US","year":2021,"indication":"High-risk early TNBC, neoadjuvant + adjuvant (KEYNOTE-522)"},{"drug":"dostarlimab","region":"US","year":2021,"indication":"dMMR recurrent/advanced endometrial cancer; dMMR solid tumours"},{"drug":"sintilimab","region":"China","year":2022,"indication":"First-line oesophageal squamous cell carcinoma with chemotherapy (ORIENT-15)"},{"drug":"serplulimab","region":"China","year":2022,"indication":"First-line ES-SCLC with chemotherapy"},{"drug":"cadonilimab","region":"China","year":2022,"indication":"Recurrent/metastatic cervical cancer after platinum"},{"drug":"relatlimab-nivolumab","region":"EU","year":2022,"indication":"Melanoma, PD-L1 <1% restriction"},{"drug":"relatlimab-nivolumab","region":"US","year":2022,"indication":"Unresectable or metastatic melanoma, age ≥12"},{"drug":"sintilimab","region":"China","year":2023,"indication":"First-line gastric or gastro-oesophageal junction adenocarcinoma with chemotherapy (ORIENT-16)"},{"drug":"pembrolizumab","region":"US","year":2023,"indication":"Locally advanced unresectable or metastatic biliary tract cancer (gallbladder cancer included) with gemcitabine and cisplatin (KEYNOTE-966)"},{"drug":"toripalimab","region":"US","year":2023,"indication":"Recurrent/metastatic nasopharyngeal carcinoma, first line with chemotherapy and later lines"},{"drug":"retifanlimab","region":"US","year":2023,"indication":"Metastatic or recurrent locally advanced Merkel cell carcinoma"},{"drug":"cadonilimab","region":"China","year":2024,"indication":"First-line persistent/recurrent/metastatic cervical cancer with chemotherapy ± bevacizumab; first-line gastric cancer with chemotherapy"},{"drug":"ivonescimab","region":"China","year":2024,"indication":"EGFR-mutant NSCLC after TKI (with chemotherapy); first-line PD-L1+ NSCLC"},{"drug":"retifanlimab","region":"EU","year":2024,"indication":"Merkel cell carcinoma"},{"drug":"dostarlimab","region":"US","year":2024,"indication":"Primary advanced/recurrent endometrial cancer with chemotherapy (all-comers)"},{"drug":"tislelizumab","region":"US","year":2024,"indication":"Second-line ESCC after chemotherapy; first-line HER2-negative gastric/GEJ with chemotherapy (PD-L1 ≥1)"},{"drug":"serplulimab","region":"EU","year":2025,"indication":"First-line ES-SCLC with carboplatin-etoposide"},{"drug":"cemiplimab","region":"US","year":2025,"indication":"Adjuvant high-risk CSCC after surgery and radiation"},{"drug":"tislelizumab","region":"US","year":2025,"indication":"First-line ESCC, PD-L1 ≥1%, with platinum chemotherapy"},{"drug":"retifanlimab","region":"US","year":2025,"indication":"Locally recurrent or metastatic anal SCC with carboplatin-paclitaxel; monotherapy after platinum"},{"drug":"penpulimab","region":"US","year":2025,"indication":"Recurrent or metastatic non-keratinising NPC with cisplatin-gemcitabine; monotherapy after platinum and ≥1 other line"},{"drug":"pembrolizumab","region":"US","year":2026,"indication":"Platinum-resistant PD-L1+ ovarian cancer; adjuvant RCC with belzutifan; with sacituzumab govitecan in 1L TNBC"},{"drug":"nivolumab","region":"US","year":2026,"indication":"Untreated advanced classical Hodgkin lymphoma with AVD, age ≥12"}],"approvedCancers":[{"id":"acral-melanoma","name":"Acral melanoma","page":"https://onco.cc/cancers/acral-melanoma/"},{"id":"advanced-small-bowel-adenocarcinoma","name":"Advanced and metastatic small bowel adenocarcinoma","page":"https://onco.cc/cancers/advanced-small-bowel-adenocarcinoma/"},{"id":"advanced-cutaneous-scc","name":"Advanced cutaneous squamous cell carcinoma","page":"https://onco.cc/cancers/advanced-cutaneous-scc/"},{"id":"hcc-advanced","name":"Advanced hepatocellular carcinoma (BCLC C)","page":"https://onco.cc/cancers/hcc-advanced/"},{"id":"advanced-melanoma","name":"Advanced melanoma (unresectable stage III and stage IV)","page":"https://onco.cc/cancers/advanced-melanoma/"},{"id":"advanced-recurrent-endometrial-cancer","name":"Advanced or recurrent endometrial cancer","page":"https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"anal","name":"Anal cancer (squamous cell carcinoma)","page":"https://onco.cc/cancers/anal/"},{"id":"basal-cell-carcinoma","name":"Basal cell carcinoma","page":"https://onco.cc/cancers/basal-cell-carcinoma/"},{"id":"urothelial","name":"Bladder & urothelial cancer","page":"https://onco.cc/cancers/urothelial/"},{"id":"cervical","name":"Cervical cancer","page":"https://onco.cc/cancers/cervical/"},{"id":"colorectal","name":"Colorectal cancer","page":"https://onco.cc/cancers/colorectal/"},{"id":"cutaneous-scc","name":"Cutaneous squamous cell carcinoma","page":"https://onco.cc/cancers/cutaneous-scc/"},{"id":"tnbc-early","name":"Early triple-negative breast cancer","page":"https://onco.cc/cancers/tnbc-early/"},{"id":"endometrial","name":"Endometrial cancer","page":"https://onco.cc/cancers/endometrial/"},{"id":"extensive-stage-sclc","name":"Extensive-stage small-cell lung cancer","page":"https://onco.cc/cancers/extensive-stage-sclc/"},{"id":"gastric","name":"Gastric & gastro-oesophageal junction cancer","page":"https://onco.cc/cancers/gastric/"},{"id":"head-and-neck","name":"Head and neck squamous cell carcinoma","page":"https://onco.cc/cancers/head-and-neck/"},{"id":"hcc","name":"Hepatocellular carcinoma","page":"https://onco.cc/cancers/hcc/"},{"id":"hodgkin-lymphoma","name":"Hodgkin lymphoma","page":"https://onco.cc/cancers/hodgkin-lymphoma/"},{"id":"hpv-negative-head-and-neck-cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","page":"https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/"},{"id":"lip-cancer","name":"Lip cancer","page":"https://onco.cc/cancers/lip-cancer/"},{"id":"locally-advanced-bcc","name":"Locally advanced and metastatic basal cell carcinoma","page":"https://onco.cc/cancers/locally-advanced-bcc/"},{"id":"locally-advanced-cervical-cancer","name":"Locally advanced cervical cancer","page":"https://onco.cc/cancers/locally-advanced-cervical-cancer/"},{"id":"locoregionally-advanced-nasopharyngeal-carcinoma","name":"Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA)","page":"https://onco.cc/cancers/locoregionally-advanced-nasopharyngeal-carcinoma/"},{"id":"melanoma","name":"Melanoma","page":"https://onco.cc/cancers/melanoma/"},{"id":"merkel-cell-carcinoma","name":"Merkel cell carcinoma","page":"https://onco.cc/cancers/merkel-cell-carcinoma/"},{"id":"mesothelioma","name":"Mesothelioma","page":"https://onco.cc/cancers/mesothelioma/"},{"id":"metastatic-anal-cancer","name":"Metastatic and recurrent anal squamous cell carcinoma","page":"https://onco.cc/cancers/metastatic-anal-cancer/"},{"id":"tnbc-metastatic","name":"Metastatic triple-negative breast cancer","page":"https://onco.cc/cancers/tnbc-metastatic/"},{"id":"gastric-msi-high","name":"Microsatellite-unstable (MSI-high) gastric cancer","page":"https://onco.cc/cancers/gastric-msi-high/"},{"id":"msi-high-pdac","name":"Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma","page":"https://onco.cc/cancers/msi-high-pdac/"},{"id":"msi-high-colorectal","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","page":"https://onco.cc/cancers/msi-high-colorectal/"},{"id":"endometrial-mmr-deficient","name":"Mismatch-repair-deficient endometrial cancer","page":"https://onco.cc/cancers/endometrial-mmr-deficient/"},{"id":"mucosal-melanoma","name":"Mucosal melanoma","page":"https://onco.cc/cancers/mucosal-melanoma/"},{"id":"nasopharyngeal","name":"Nasopharyngeal carcinoma","page":"https://onco.cc/cancers/nasopharyngeal/"},{"id":"nsclc","name":"Non-small-cell lung cancer","page":"https://onco.cc/cancers/nsclc/"},{"id":"esophageal","name":"Oesophageal cancer","page":"https://onco.cc/cancers/esophageal/"},{"id":"ovarian","name":"Ovarian cancer","page":"https://onco.cc/cancers/ovarian/"},{"id":"pancreatic","name":"Pancreatic ductal adenocarcinoma","page":"https://onco.cc/cancers/pancreatic/"},{"id":"gastric-pdl1-high","name":"PD-L1-high gastric cancer","page":"https://onco.cc/cancers/gastric-pdl1-high/"},{"id":"pdl1-high-nsclc","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","page":"https://onco.cc/cancers/pdl1-high-nsclc/"},{"id":"platinum-resistant-ovarian-cancer","name":"Platinum-resistant ovarian cancer","page":"https://onco.cc/cancers/platinum-resistant-ovarian-cancer/"},{"id":"primary-mediastinal-b-cell-lymphoma","name":"Primary mediastinal (thymic) large B-cell lymphoma","page":"https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"rectal-cancer","name":"Rectal cancer","page":"https://onco.cc/cancers/rectal-cancer/"},{"id":"recurrent-metastatic-nasopharyngeal-carcinoma","name":"Recurrent and metastatic nasopharyngeal carcinoma","page":"https://onco.cc/cancers/recurrent-metastatic-nasopharyngeal-carcinoma/"},{"id":"recurrent-metastatic-cervical-cancer","name":"Recurrent or metastatic cervical cancer","page":"https://onco.cc/cancers/recurrent-metastatic-cervical-cancer/"},{"id":"recurrent-metastatic-hnscc","name":"Recurrent or metastatic head and neck squamous cell carcinoma","page":"https://onco.cc/cancers/recurrent-metastatic-hnscc/"},{"id":"relapsed-refractory-hodgkin-lymphoma","name":"Relapsed and refractory classical Hodgkin lymphoma","page":"https://onco.cc/cancers/relapsed-refractory-hodgkin-lymphoma/"},{"id":"rcc","name":"Renal cell carcinoma","page":"https://onco.cc/cancers/rcc/"},{"id":"resectable-nsclc","name":"Resectable stage I to III non-small-cell lung cancer","page":"https://onco.cc/cancers/resectable-nsclc/"},{"id":"sclc","name":"Small-cell lung cancer","page":"https://onco.cc/cancers/sclc/"},{"id":"stage-ii-melanoma","name":"Stage IIB and IIC melanoma","page":"https://onco.cc/cancers/stage-ii-melanoma/"},{"id":"stage-iii-melanoma","name":"Stage III melanoma (after surgery)","page":"https://onco.cc/cancers/stage-iii-melanoma/"},{"id":"tnbc","name":"Triple-negative breast cancer (TNBC)","page":"https://onco.cc/cancers/tnbc/"},{"id":"uterine-carcinosarcoma","name":"Uterine carcinosarcoma","page":"https://onco.cc/cancers/uterine-carcinosarcoma/"},{"id":"vaginal-adenocarcinoma","name":"Vaginal adenocarcinoma (including DES-associated clear cell adenocarcinoma)","page":"https://onco.cc/cancers/vaginal-adenocarcinoma/"}],"trials":716,"pipelineNotes":[],"discontinued":[]},{"id":"ctla4","label":"CTLA-4","symbol":"CTLA4","hgnc":"HGNC:2505","side":"immune-cell","target":"https://onco.cc/targets/ctla4/","page":"https://onco.cc/checkpoints/immune/#ctla4","expressedOn":{"text":"Activated T cells, at 30- to 50-fold lower surface levels than CD28; widely expressed with the highest levels in lymphoid tissues.","source":{"label":"UniProt P16410","url":"https://www.uniprot.org/uniprotkb/P16410/entry"}},"partners":["cd80","cd86"],"bestStatus":{"status":"approved","drug":"ipilimumab"},"drugs":[{"id":"ipilimumab","name":"Ipilimumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/ipilimumab/"},{"id":"tremelimumab","name":"Tremelimumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/tremelimumab/"},{"id":"botensilimab","name":"Botensilimab","drugClass":"antibody","status":"phase-2","note":"Fc-enhanced","page":"https://onco.cc/drugs/botensilimab/"},{"id":"gotistobart","name":"Gotistobart","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/gotistobart/"},{"id":"cadonilimab","name":"Cadonilimab","drugClass":"bispecific","status":"approved","note":"PD-1 x CTLA-4","page":"https://onco.cc/drugs/cadonilimab/"},{"id":"iparomlimab-tuvonralimab","name":"Iparomlimab and tuvonralimab","drugClass":"antibody","status":"approved","note":"anti-PD-1 and anti-CTLA-4 mixture","page":"https://onco.cc/drugs/iparomlimab-tuvonralimab/"},{"id":"adg126","name":"ADG126","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/adg126/"},{"id":"ba3071","name":"BA3071","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/ba3071/"},{"id":"bcd-217","name":"BCD-217","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/bcd-217/"},{"id":"jk08","name":"JK08","drugClass":"fusion-protein","status":"phase-2","page":"https://onco.cc/drugs/jk08/"},{"id":"lorigerlimab","name":"Lorigerlimab","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/lorigerlimab/"}],"approvals":[{"drug":"ipilimumab","region":"US","year":2011,"indication":"Metastatic melanoma"},{"drug":"cadonilimab","region":"China","year":2022,"indication":"Recurrent/metastatic cervical cancer after platinum"},{"drug":"tremelimumab","region":"US","year":2022,"indication":"Metastatic NSCLC without EGFR/ALK, with durvalumab and platinum chemotherapy; unresectable HCC with durvalumab"},{"drug":"cadonilimab","region":"China","year":2024,"indication":"First-line persistent/recurrent/metastatic cervical cancer with chemotherapy ± bevacizumab; first-line gastric cancer with chemotherapy"},{"drug":"iparomlimab-tuvonralimab","region":"CN","year":2024,"indication":"Recurrent or metastatic cervical cancer after platinum chemotherapy"}],"approvedCancers":[{"id":"acral-melanoma","name":"Acral melanoma","page":"https://onco.cc/cancers/acral-melanoma/"},{"id":"hcc-advanced","name":"Advanced hepatocellular carcinoma (BCLC C)","page":"https://onco.cc/cancers/hcc-advanced/"},{"id":"advanced-melanoma","name":"Advanced melanoma (unresectable stage III and stage IV)","page":"https://onco.cc/cancers/advanced-melanoma/"},{"id":"cervical","name":"Cervical cancer","page":"https://onco.cc/cancers/cervical/"},{"id":"colorectal","name":"Colorectal cancer","page":"https://onco.cc/cancers/colorectal/"},{"id":"gastric","name":"Gastric & gastro-oesophageal junction cancer","page":"https://onco.cc/cancers/gastric/"},{"id":"hcc","name":"Hepatocellular carcinoma","page":"https://onco.cc/cancers/hcc/"},{"id":"limited-stage-sclc","name":"Limited-stage small-cell lung cancer","page":"https://onco.cc/cancers/limited-stage-sclc/"},{"id":"melanoma","name":"Melanoma","page":"https://onco.cc/cancers/melanoma/"},{"id":"mesothelioma","name":"Mesothelioma","page":"https://onco.cc/cancers/mesothelioma/"},{"id":"msi-high-colorectal","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","page":"https://onco.cc/cancers/msi-high-colorectal/"},{"id":"mucosal-melanoma","name":"Mucosal melanoma","page":"https://onco.cc/cancers/mucosal-melanoma/"},{"id":"nsclc","name":"Non-small-cell lung cancer","page":"https://onco.cc/cancers/nsclc/"},{"id":"rcc","name":"Renal cell carcinoma","page":"https://onco.cc/cancers/rcc/"},{"id":"stage-iii-melanoma","name":"Stage III melanoma (after surgery)","page":"https://onco.cc/cancers/stage-iii-melanoma/"}],"trials":103,"pipelineNotes":[],"discontinued":[]},{"id":"lag3","label":"LAG-3","symbol":"LAG3","hgnc":"HGNC:6476","side":"immune-cell","target":"https://onco.cc/targets/lag3/","page":"https://onco.cc/checkpoints/immune/#lag3","expressedOn":{"text":"Primarily activated T cells and a subset of NK cells.","source":{"label":"UniProt P18627","url":"https://www.uniprot.org/uniprotkb/P18627/entry"}},"partners":["hla-dra","fgl1"],"bestStatus":{"status":"approved","drug":"relatlimab-nivolumab"},"drugs":[{"id":"relatlimab-nivolumab","name":"Relatlimab + nivolumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/relatlimab-nivolumab/"},{"id":"fianlimab","name":"Fianlimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/fianlimab/"},{"id":"favezelimab","name":"Favezelimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/favezelimab/"},{"id":"hlx26","name":"HLX26","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/hlx26/"}],"approvals":[{"drug":"relatlimab-nivolumab","region":"EU","year":2022,"indication":"Melanoma, PD-L1 <1% restriction"},{"drug":"relatlimab-nivolumab","region":"US","year":2022,"indication":"Unresectable or metastatic melanoma, age ≥12"}],"approvedCancers":[{"id":"advanced-melanoma","name":"Advanced melanoma (unresectable stage III and stage IV)","page":"https://onco.cc/cancers/advanced-melanoma/"},{"id":"melanoma","name":"Melanoma","page":"https://onco.cc/cancers/melanoma/"}],"trials":24,"pipelineNotes":[],"discontinued":[]},{"id":"tim3","label":"TIM-3","symbol":"HAVCR2","hgnc":"HGNC:18437","side":"immune-cell","target":"https://onco.cc/targets/tim3/","page":"https://onco.cc/checkpoints/immune/#tim3","expressedOn":{"text":"Th1 lymphocytes, regulatory T cells after TCR stimulation, dendritic cells and NK cells; also epithelial tissues.","source":{"label":"UniProt Q8TDQ0","url":"https://www.uniprot.org/uniprotkb/Q8TDQ0/entry"}},"partners":["lgals9","ceacam1"],"bestStatus":{"status":"phase-3","drug":"cobolimab"},"drugs":[{"id":"cobolimab","name":"Cobolimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/cobolimab/"},{"id":"sabatolimab","name":"Sabatolimab","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/sabatolimab/"},{"id":"azd7789","name":"AZD7789","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/azd7789/"},{"id":"lb1410","name":"LB1410","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/lb1410/"}],"approvals":[],"approvedCancers":[],"trials":5,"pipelineNotes":[],"discontinued":[{"name":"Sabatolimab (MBG453)","reason":"In December 2023 Novartis decided to terminate the sabatolimab clinical development programme early after the phase 2 (STIMULUS MDS1) and phase 3 (STIMULUS MDS2) studies failed to meet their primary objectives; not due to safety concerns.","source":{"label":"ClinicalTrials.gov NCT04266301","url":"https://clinicaltrials.gov/study/NCT04266301"}}]},{"id":"tigit","label":"TIGIT","symbol":"TIGIT","hgnc":"HGNC:26838","side":"immune-cell","target":"https://onco.cc/targets/tigit/","page":"https://onco.cc/checkpoints/immune/#tigit","expressedOn":{"text":"Low levels on peripheral memory and regulatory CD4 T cells and NK cells, up-regulated on activation (protein level).","source":{"label":"UniProt Q495A1","url":"https://www.uniprot.org/uniprotkb/Q495A1/entry"}},"partners":["pvr","nectin2"],"bestStatus":{"status":"phase-3","drug":"domvanalimab"},"drugs":[{"id":"tiragolumab","name":"Tiragolumab","drugClass":"antibody","status":"negative","page":"https://onco.cc/drugs/tiragolumab/"},{"id":"domvanalimab","name":"Domvanalimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/domvanalimab/"},{"id":"vibostolimab","name":"Vibostolimab","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/vibostolimab/"},{"id":"rilvegostomig","name":"Rilvegostomig","drugClass":"bispecific","status":"phase-2","note":"PD-1 x TIGIT","page":"https://onco.cc/drugs/rilvegostomig/"},{"id":"hb0036","name":"HB0036","drugClass":"fusion-protein","status":"phase-2","page":"https://onco.cc/drugs/hb0036/"}],"approvals":[],"approvedCancers":[],"trials":38,"pipelineNotes":[],"discontinued":[{"name":"Tiragolumab (SKYSCRAPER programme)","reason":"The sponsor's decision was based on the negative results of SKYSCRAPER-02.","source":{"label":"ClinicalTrials.gov NCT04308785","url":"https://clinicaltrials.gov/study/NCT04308785"}},{"name":"Vibostolimab (MK-7684A-007)","reason":"Terminated early due to futility.","source":{"label":"ClinicalTrials.gov NCT05226598","url":"https://clinicaltrials.gov/study/NCT05226598"}},{"name":"Domvanalimab in gastro-oesophageal cancer","reason":"The interim analysis of STAR-221 showed that the domvanalimab combination did not improve overall survival compared with standard of care.","source":{"label":"ClinicalTrials.gov NCT07134556","url":"https://clinicaltrials.gov/study/NCT07134556"}}]},{"id":"btla","label":"BTLA","symbol":"BTLA","hgnc":"HGNC:21087","side":"immune-cell","target":"https://onco.cc/targets/btla/","page":"https://onco.cc/checkpoints/immune/#btla","expressedOn":{"text":"Lymphocytes; an inhibitory receptor that dampens antigen-receptor signalling through SHP-1 and SHP-2.","source":{"label":"UniProt Q7Z6A9","url":"https://www.uniprot.org/uniprotkb/Q7Z6A9/entry"}},"partners":["tnfrsf14"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"Tifcemalimab (anti-BTLA) with toripalimab is in a phase 3 consolidation study in small-cell lung cancer (recruiting).","source":{"label":"ClinicalTrials.gov NCT06095583","url":"https://clinicaltrials.gov/study/NCT06095583"}}],"discontinued":[]},{"id":"vista","label":"VISTA","symbol":"VSIR","hgnc":"HGNC:30085","side":"immune-cell","target":"https://onco.cc/targets/vista/","page":"https://onco.cc/checkpoints/immune/#vista","expressedOn":{"text":"Myeloid cells including CD11b monocytes and CD66b neutrophils, at low levels on CD4 and CD8 T cells and a subset of NK cells; not on B cells (protein level).","source":{"label":"UniProt Q9H7M9","url":"https://www.uniprot.org/uniprotkb/Q9H7M9/entry"}},"partners":[],"partnerNote":{"text":"Ligands are not settled; the receptor inhibits the T-cell response.","source":{"label":"UniProt Q9H7M9","url":"https://www.uniprot.org/uniprotkb/Q9H7M9/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"HMBD-002 (anti-VISTA) completed a phase 1 study alone and with pembrolizumab.","source":{"label":"ClinicalTrials.gov NCT05082610","url":"https://clinicaltrials.gov/study/NCT05082610"}},{"text":"CI-8993 (anti-VISTA) completed a phase 1 study in advanced solid tumours.","source":{"label":"ClinicalTrials.gov NCT04475523","url":"https://clinicaltrials.gov/study/NCT04475523"}}],"discontinued":[]},{"id":"klrc1","label":"NKG2A","symbol":"KLRC1","hgnc":"HGNC:6374","side":"immune-cell","target":"https://onco.cc/targets/klrc1/","page":"https://onco.cc/checkpoints/immune/#klrc1","expressedOn":{"text":"Predominantly NK cells, with CD94; subsets of intraepithelial and memory CD8 T cells (protein level).","source":{"label":"UniProt P26715","url":"https://www.uniprot.org/uniprotkb/P26715/entry"}},"partners":["hla-e"],"bestStatus":{"status":"phase-3","drug":"monalizumab"},"drugs":[{"id":"monalizumab","name":"Monalizumab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/monalizumab/"}],"approvals":[],"approvedCancers":[],"trials":4,"pipelineNotes":[],"discontinued":[]},{"id":"kir2dl1","label":"KIR (KIR2DL1/2/3)","symbol":"KIR2DL1","hgnc":"HGNC:6329","side":"immune-cell","target":"https://onco.cc/targets/kir2dl1/","page":"https://onco.cc/checkpoints/immune/#kir2dl1","expressedOn":{"text":"NK cells; receptors for HLA-C alleles that inhibit NK-cell lysis.","source":{"label":"UniProt P43626","url":"https://www.uniprot.org/uniprotkb/P43626/entry"}},"partners":[],"partnerNote":{"text":"HLA-C group 2 alleles (KIR2DL1) and HLA-Cw1, Cw3, Cw7 (KIR2DL3).","source":{"label":"UniProt P43628","url":"https://www.uniprot.org/uniprotkb/P43628/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"Lirilumab (anti-KIR2DL1/2/3) reached phase 1/2 with nivolumab in solid tumours.","source":{"label":"ClinicalTrials.gov NCT01714739","url":"https://clinicaltrials.gov/study/NCT01714739"}}],"discontinued":[{"name":"Lirilumab in myeloid malignancies","reason":"Enrolment was stopped after the sponsor's decision not to pursue the development of lirilumab for myeloid malignancies.","source":{"label":"ClinicalTrials.gov NCT02599649","url":"https://clinicaltrials.gov/study/NCT02599649"}}]},{"id":"cd96","label":"CD96","symbol":"CD96","hgnc":"HGNC:16892","side":"immune-cell","target":"https://onco.cc/targets/cd96/","page":"https://onco.cc/checkpoints/immune/#cd96","expressedOn":{"text":"Activated T and NK cells; expressed on normal T-cell lines and clones and at very low levels on activated B cells.","source":{"label":"UniProt P40200","url":"https://www.uniprot.org/uniprotkb/P40200/entry"}},"partners":["pvr"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"GSK6097608 (anti-CD96) is in phase 2 platform studies with dostarlimab in non-small-cell lung cancer.","source":{"label":"ClinicalTrials.gov NCT05565378","url":"https://clinicaltrials.gov/study/NCT05565378"}}],"discontinued":[]},{"id":"pvrig","label":"PVRIG (CD112R)","symbol":"PVRIG","hgnc":"HGNC:32190","side":"immune-cell","target":"https://onco.cc/targets/pvrig/","page":"https://onco.cc/checkpoints/immune/#pvrig","expressedOn":{"text":"Low levels on freshly isolated T and NK cells, predominantly memory and effector CD8 T cells and both CD16-positive and CD16-negative NK cells; not on B cells, naive or helper T cells, monocytes or neutrophils (protein level).","source":{"label":"UniProt Q6DKI7","url":"https://www.uniprot.org/uniprotkb/Q6DKI7/entry"}},"partners":["nectin2"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"COM701 (anti-PVRIG) completed phase 1/2 with a TIGIT antibody and nivolumab and is recruiting in platinum-sensitive ovarian cancer.","source":{"label":"ClinicalTrials.gov NCT06888921","url":"https://clinicaltrials.gov/study/NCT06888921"}}],"discontinued":[]}]},{"id":"ligand","name":"Their ligands on tumour and antigen-presenting cells","tone":"ligand","plain":"The other half of each pair. Tumours borrow these molecules from normal tissue so that the brakes on nearby T cells are pressed. Blocking the ligand works as well as blocking the receptor for PD-1.","members":[{"id":"pdl1","label":"PD-L1","symbol":"CD274","hgnc":"HGNC:17635","side":"tumour-or-apc","target":"https://onco.cc/targets/pdl1/","page":"https://onco.cc/checkpoints/immune/#pdl1","expressedOn":{"text":"Activated T and B cells, dendritic cells, keratinocytes and monocytes; widely expressed in tissue, highest in lung, liver and pituitary.","source":{"label":"UniProt Q9NZQ7","url":"https://www.uniprot.org/uniprotkb/Q9NZQ7/entry"}},"partners":["pd1"],"bestStatus":{"status":"approved","drug":"atezolizumab"},"drugs":[{"id":"atezolizumab","name":"Atezolizumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/atezolizumab/"},{"id":"durvalumab","name":"Durvalumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/durvalumab/"},{"id":"avelumab","name":"Avelumab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/avelumab/"},{"id":"cosibelimab","name":"Cosibelimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/cosibelimab/"},{"id":"sugemalimab","name":"Sugemalimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/sugemalimab/"},{"id":"envafolimab","name":"Envafolimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/envafolimab/"},{"id":"adebrelimab","name":"Adebrelimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/adebrelimab/"},{"id":"benmelstobart","name":"Benmelstobart","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/benmelstobart/"},{"id":"socazolimab","name":"Socazolimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/socazolimab/"},{"id":"acasunlimab","name":"Acasunlimab","drugClass":"bispecific","status":"phase-3","note":"PD-L1 x 4-1BB","page":"https://onco.cc/drugs/acasunlimab/"},{"id":"retlirafusp-alfa","name":"Retlirafusp alfa","drugClass":"fusion-protein","status":"phase-3","note":"PD-L1 antibody fused to a TGF-beta receptor II trap","page":"https://onco.cc/drugs/retlirafusp-alfa/"},{"id":"io102-io103","name":"IO102-IO103","drugClass":"vaccine","status":"phase-3","note":"PD-L1 and IDO peptide vaccine","page":"https://onco.cc/drugs/io102-io103/"},{"id":"hb0036","name":"HB0036","drugClass":"fusion-protein","status":"phase-2","page":"https://onco.cc/drugs/hb0036/"},{"id":"hlx43","name":"HLX43","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/hlx43/"},{"id":"iparomlimab-tuvonralimab","name":"Iparomlimab and tuvonralimab","drugClass":"antibody","status":"approved","page":"https://onco.cc/drugs/iparomlimab-tuvonralimab/"},{"id":"pf-08046054","name":"PF-08046054","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/pf-08046054/"},{"id":"pm8002","name":"PM8002","drugClass":"bispecific","status":"phase-3","page":"https://onco.cc/drugs/pm8002/"},{"id":"sasanlimab","name":"Sasanlimab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/sasanlimab/"},{"id":"ssgj-706","name":"SSGJ-706","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/ssgj-706/"},{"id":"t3011","name":"T3011","drugClass":"small-molecule","status":"phase-2","page":"https://onco.cc/drugs/t3011/"},{"id":"tiragolumab","name":"Tiragolumab","drugClass":"cell-therapy","status":"negative","page":"https://onco.cc/drugs/tiragolumab/"},{"id":"tqb2450","name":"TQB2450","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/tqb2450/"}],"approvals":[{"drug":"atezolizumab","region":"US","year":2016,"indication":"Urothelial carcinoma (later withdrawn); NSCLC"},{"drug":"durvalumab","region":"US","year":2017,"indication":"Locally advanced or metastatic urothelial carcinoma after platinum (accelerated; indication withdrawn 2021)"},{"drug":"avelumab","region":"US","year":2017,"indication":"Merkel cell carcinoma; urothelial cancer after platinum (accelerated)"},{"drug":"durvalumab","region":"US","year":2018,"indication":"Unresectable stage III NSCLC after chemoradiation"},{"drug":"avelumab","region":"US","year":2020,"indication":"Maintenance after first-line platinum in advanced urothelial cancer"},{"drug":"sugemalimab","region":"China","year":2021,"indication":"First-line metastatic squamous and non-squamous NSCLC with platinum chemotherapy (GEMSTONE-302)"},{"drug":"envafolimab","region":"China","year":2021,"indication":"Previously treated MSI-H or dMMR advanced solid tumours"},{"drug":"sugemalimab","region":"China","year":2022,"indication":"Unresectable stage III NSCLC without progression after chemoradiotherapy (GEMSTONE-301)"},{"drug":"durvalumab","region":"US","year":2022,"indication":"Locally advanced or metastatic biliary tract cancer (gallbladder cancer included) with gemcitabine and cisplatin (TOPAZ-1)"},{"drug":"adebrelimab","region":"China","year":2023,"indication":"First-line extensive-stage small cell lung cancer with carboplatin and etoposide (CAPSTONE-1)"},{"drug":"benmelstobart","region":"CN","year":2024,"indication":"Extensive-stage small-cell lung cancer, first line, with anlotinib and platinum-etoposide chemotherapy"},{"drug":"sugemalimab","region":"EU","year":2024,"indication":"First-line metastatic NSCLC with platinum chemotherapy, no sensitising EGFR, ALK, ROS1 or RET alterations"},{"drug":"durvalumab","region":"UK","year":2024,"indication":"Locally advanced, unresectable or metastatic biliary tract cancer with gemcitabine and cisplatin; NICE TA944 recommended 10 January 2024 with a commercial arrangement"},{"drug":"cosibelimab","region":"US","year":2024,"indication":"Metastatic or locally advanced cutaneous SCC not curable by surgery or radiation"},{"drug":"atezolizumab","region":"US","year":2026,"indication":"Adjuvant muscle-invasive bladder cancer, ctDNA-positive after cystectomy"},{"drug":"durvalumab","region":"US","year":2026,"indication":"High-risk NMIBC with BCG"}],"approvedCancers":[{"id":"advanced-cutaneous-scc","name":"Advanced cutaneous squamous cell carcinoma","page":"https://onco.cc/cancers/advanced-cutaneous-scc/"},{"id":"hcc-advanced","name":"Advanced hepatocellular carcinoma (BCLC C)","page":"https://onco.cc/cancers/hcc-advanced/"},{"id":"advanced-recurrent-endometrial-cancer","name":"Advanced or recurrent endometrial cancer","page":"https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"alveolar-soft-part-sarcoma","name":"Alveolar soft part sarcoma","page":"https://onco.cc/cancers/alveolar-soft-part-sarcoma/"},{"id":"cholangiocarcinoma","name":"Biliary tract cancer (cholangiocarcinoma)","page":"https://onco.cc/cancers/cholangiocarcinoma/"},{"id":"urothelial","name":"Bladder & urothelial cancer","page":"https://onco.cc/cancers/urothelial/"},{"id":"cancer-of-unknown-primary","name":"Cancer of unknown primary (CUP)","page":"https://onco.cc/cancers/cancer-of-unknown-primary/"},{"id":"colorectal","name":"Colorectal cancer","page":"https://onco.cc/cancers/colorectal/"},{"id":"cutaneous-scc","name":"Cutaneous squamous cell carcinoma","page":"https://onco.cc/cancers/cutaneous-scc/"},{"id":"extensive-stage-sclc","name":"Extensive-stage small-cell lung cancer","page":"https://onco.cc/cancers/extensive-stage-sclc/"},{"id":"extrahepatic-cholangiocarcinoma","name":"Extrahepatic cholangiocarcinoma (perihilar and distal)","page":"https://onco.cc/cancers/extrahepatic-cholangiocarcinoma/"},{"id":"gastric","name":"Gastric & gastro-oesophageal junction cancer","page":"https://onco.cc/cancers/gastric/"},{"id":"hcc","name":"Hepatocellular carcinoma","page":"https://onco.cc/cancers/hcc/"},{"id":"hcc-intermediate","name":"Intermediate hepatocellular carcinoma (BCLC B)","page":"https://onco.cc/cancers/hcc-intermediate/"},{"id":"intrahepatic-cholangiocarcinoma","name":"Intrahepatic cholangiocarcinoma","page":"https://onco.cc/cancers/intrahepatic-cholangiocarcinoma/"},{"id":"limited-stage-sclc","name":"Limited-stage small-cell lung cancer","page":"https://onco.cc/cancers/limited-stage-sclc/"},{"id":"merkel-cell-carcinoma","name":"Merkel cell carcinoma","page":"https://onco.cc/cancers/merkel-cell-carcinoma/"},{"id":"tnbc-metastatic","name":"Metastatic triple-negative breast cancer","page":"https://onco.cc/cancers/tnbc-metastatic/"},{"id":"nsclc","name":"Non-small-cell lung cancer","page":"https://onco.cc/cancers/nsclc/"},{"id":"pdl1-high-nsclc","name":"PD-L1-high non-small-cell lung cancer without a driver mutation","page":"https://onco.cc/cancers/pdl1-high-nsclc/"},{"id":"peripheral-t-cell-lymphoma","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","page":"https://onco.cc/cancers/peripheral-t-cell-lymphoma/"},{"id":"rcc","name":"Renal cell carcinoma","page":"https://onco.cc/cancers/rcc/"},{"id":"resectable-nsclc","name":"Resectable stage I to III non-small-cell lung cancer","page":"https://onco.cc/cancers/resectable-nsclc/"},{"id":"sclc","name":"Small-cell lung cancer","page":"https://onco.cc/cancers/sclc/"},{"id":"tnbc","name":"Triple-negative breast cancer (TNBC)","page":"https://onco.cc/cancers/tnbc/"},{"id":"stage-iii-unresectable-nsclc","name":"Unresectable stage III non-small-cell lung cancer","page":"https://onco.cc/cancers/stage-iii-unresectable-nsclc/"}],"trials":322,"pipelineNotes":[],"discontinued":[]},{"id":"pdcd1lg2","label":"PD-L2","symbol":"PDCD1LG2","hgnc":"HGNC:18731","side":"tumour-or-apc","target":"https://onco.cc/targets/pdcd1lg2/","page":"https://onco.cc/checkpoints/immune/#pdcd1lg2","expressedOn":{"text":"Highly expressed in heart, placenta, pancreas, lung and liver; weakly in spleen, lymph nodes and thymus.","source":{"label":"UniProt Q9BQ51","url":"https://www.uniprot.org/uniprotkb/Q9BQ51/entry"}},"partners":["pd1"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"cd80","label":"CD80 (B7-1)","symbol":"CD80","hgnc":"HGNC:1700","side":"tumour-or-apc","target":"https://onco.cc/targets/cd80/","page":"https://onco.cc/checkpoints/immune/#cd80","expressedOn":{"text":"The surface of antigen-presenting cells.","source":{"label":"UniProt P33681","url":"https://www.uniprot.org/uniprotkb/P33681/entry"}},"partners":["ctla4","cd28"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"cd86","label":"CD86 (B7-2)","symbol":"CD86","hgnc":"HGNC:1705","side":"tumour-or-apc","target":"https://onco.cc/targets/cd86/","page":"https://onco.cc/checkpoints/immune/#cd86","expressedOn":{"text":"The surface of antigen-presenting cells.","source":{"label":"UniProt P42081","url":"https://www.uniprot.org/uniprotkb/P42081/entry"}},"partners":["ctla4","cd28"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"hla-dra","label":"MHC class II (HLA-DR)","symbol":"HLA-DRA","hgnc":"HGNC:4947","side":"tumour-or-apc","target":"https://onco.cc/targets/hla-dra/","page":"https://onco.cc/checkpoints/immune/#hla-dra","expressedOn":{"text":"Professional antigen-presenting cells: macrophages, dendritic cells and B cells; thymic epithelial cells (protein level).","source":{"label":"UniProt P01903","url":"https://www.uniprot.org/uniprotkb/P01903/entry"}},"partners":["lag3"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"fgl1","label":"FGL1","symbol":"FGL1","hgnc":"HGNC:3695","side":"soluble","target":"https://onco.cc/targets/fgl1/","page":"https://onco.cc/checkpoints/immune/#fgl1","expressedOn":{"text":"Liver-specific under normal conditions; secreted by hepatocytes and certain tumour cells, and binds LAG-3 independently of MHC class II.","source":{"label":"UniProt Q08830","url":"https://www.uniprot.org/uniprotkb/Q08830/entry"}},"partners":["lag3"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"lgals9","label":"Galectin-9","symbol":"LGALS9","hgnc":"HGNC:6570","side":"tumour-or-apc","target":"https://onco.cc/targets/lgals9/","page":"https://onco.cc/checkpoints/immune/#lgals9","expressedOn":{"text":"Peripheral blood leukocytes and lymphatic tissues; lung, liver, breast and kidney, with higher levels in tumour endothelial cells than normal endothelium (protein level).","source":{"label":"UniProt O00182","url":"https://www.uniprot.org/uniprotkb/O00182/entry"}},"partners":["tim3"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"ceacam1","label":"CEACAM1","symbol":"CEACAM1","hgnc":"HGNC:1814","side":"tumour-or-apc","target":"https://onco.cc/targets/ceacam1/","page":"https://onco.cc/checkpoints/immune/#ceacam1","expressedOn":{"text":"Columnar epithelial cells of the colon (protein level); granulocytes and lymphocytes, T cells carrying the long cytoplasmic isoforms.","source":{"label":"UniProt P13688","url":"https://www.uniprot.org/uniprotkb/P13688/entry"}},"partners":["tim3"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"pvr","label":"CD155 (PVR)","symbol":"PVR","hgnc":"HGNC:9705","side":"tumour-or-apc","target":"https://onco.cc/targets/pvr/","page":"https://onco.cc/checkpoints/immune/#pvr","expressedOn":{"text":"Barely or weakly expressed in normal human tissues but frequently over-expressed in malignant tumours; the ligand for the co-stimulatory receptor CD226 and the co-inhibitory receptors TIGIT and CD96 on NK and T cells.","source":{"label":"Kučan Brlić et al. 2017, Cell Mol Immunol: CD155, an onco-immunologic molecule","url":"https://europepmc.org/article/MED/28730595"}},"partners":["tigit","cd96"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"nectin2","label":"CD112 (nectin-2)","symbol":"NECTIN2","hgnc":"HGNC:9707","side":"tumour-or-apc","target":"https://onco.cc/targets/nectin2/","page":"https://onco.cc/checkpoints/immune/#nectin2","expressedOn":{"text":"Ubiquitous; a co-stimulator through CD226 and a co-inhibitor through PVRIG, the two binding competitively.","source":{"label":"UniProt Q92692","url":"https://www.uniprot.org/uniprotkb/Q92692/entry"}},"partners":["tigit","pvrig"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"tnfrsf14","label":"HVEM","symbol":"TNFRSF14","hgnc":"HGNC:11912","side":"tumour-or-apc","target":"https://onco.cc/targets/tnfrsf14/","page":"https://onco.cc/checkpoints/immune/#tnfrsf14","expressedOn":{"text":"Widely expressed, highest in lung, spleen and thymus; a subpopulation of B cells and monocytes, and naive T cells.","source":{"label":"UniProt Q92956","url":"https://www.uniprot.org/uniprotkb/Q92956/entry"}},"partners":["btla"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"hla-e","label":"HLA-E","symbol":"HLA-E","hgnc":"HGNC:4962","side":"tumour-or-apc","target":"https://onco.cc/targets/hla-e/","page":"https://onco.cc/checkpoints/immune/#hla-e","expressedOn":{"text":"Endothelial cells of all vessel types outside lymphoid tissue; in lymphoid organs, endothelial venules, B and T cells, monocytes, macrophages, NK cells and megakaryocytes (protein level).","source":{"label":"UniProt P13747","url":"https://www.uniprot.org/uniprotkb/P13747/entry"}},"partners":["klrc1"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]}]},{"id":"innate","name":"Innate 'don't eat me' checkpoints","tone":"innate","plain":"Signals a cell shows to macrophages to say it is self and should not be eaten. Tumours over-express them; blocking the pair lets macrophages engulf the cancer cell.","evidence":{"text":"The CD24-Siglec-10 interaction inhibits macrophage-mediated phagocytosis as well as NK-cell cytotoxicity.","source":{"label":"Panagiotou et al. 2022, Cancers: CD24 as a target for cancer immunotherapy","url":"https://europepmc.org/article/MED/36013184"}},"members":[{"id":"cd47","label":"CD47","symbol":"CD47","hgnc":"HGNC:1682","side":"tumour-or-apc","target":"https://onco.cc/targets/cd47/","page":"https://onco.cc/checkpoints/immune/#cd47","expressedOn":{"text":"Very broadly distributed on normal adult tissues as well as ovarian tumours, especially abundant in some epithelia and the brain.","source":{"label":"UniProt Q08722","url":"https://www.uniprot.org/uniprotkb/Q08722/entry"}},"partners":["sirpa"],"bestStatus":{"status":"phase-3","drug":"evorpacept"},"drugs":[{"id":"magrolimab","name":"Magrolimab","drugClass":"antibody","status":"withdrawn","page":"https://onco.cc/drugs/magrolimab/"},{"id":"evorpacept","name":"Evorpacept","drugClass":"fusion-protein","status":"phase-3","note":"SIRP-alpha Fc fusion that binds CD47","page":"https://onco.cc/drugs/evorpacept/"},{"id":"peluntamig","name":"Peluntamig","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/peluntamig/"},{"id":"spevatamig","name":"Spevatamig","drugClass":"bispecific","status":"phase-2","page":"https://onco.cc/drugs/spevatamig/"}],"approvals":[],"approvedCancers":[],"trials":9,"pipelineNotes":[],"discontinued":[{"name":"Magrolimab with azacitidine in higher-risk MDS (ENHANCE)","reason":"Study discontinued due to futility based on a planned analysis.","source":{"label":"ClinicalTrials.gov NCT04313881","url":"https://clinicaltrials.gov/study/NCT04313881"}},{"name":"Magrolimab programme in MDS","reason":"Termination due to discontinuation of magrolimab development in MDS.","source":{"label":"ClinicalTrials.gov NCT05835011","url":"https://clinicaltrials.gov/study/NCT05835011"}}]},{"id":"sirpa","label":"SIRP-alpha","symbol":"SIRPA","hgnc":"HGNC:9662","side":"macrophage","target":"https://onco.cc/targets/sirpa/","page":"https://onco.cc/checkpoints/immune/#sirpa","expressedOn":{"text":"Myeloid cells but not T cells; ubiquitous at lower levels, highly expressed in brain.","source":{"label":"UniProt P78324","url":"https://www.uniprot.org/uniprotkb/P78324/entry"}},"partners":["cd47"],"bestStatus":{"status":"phase-3","drug":"evorpacept"},"drugs":[{"id":"evorpacept","name":"Evorpacept","drugClass":"fusion-protein","status":"phase-3","note":"the receptor's own binding domain, given as a decoy","page":"https://onco.cc/drugs/evorpacept/"}],"approvals":[],"approvedCancers":[],"trials":4,"pipelineNotes":[],"discontinued":[]},{"id":"cd24","label":"CD24","symbol":"CD24","hgnc":"HGNC:1645","side":"tumour-or-apc","target":"https://onco.cc/targets/cd24/","page":"https://onco.cc/checkpoints/immune/#cd24","expressedOn":{"text":"B cells and the T-cell surface; erythroleukaemia and small-cell lung carcinoma cell lines.","source":{"label":"UniProt P25063","url":"https://www.uniprot.org/uniprotkb/P25063/entry"}},"partners":["siglec10"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"IMM47 (anti-CD24) entered a phase 1 study in advanced solid tumours; the registry status is unknown.","source":{"label":"ClinicalTrials.gov NCT05985083","url":"https://clinicaltrials.gov/study/NCT05985083"}}],"discontinued":[]},{"id":"siglec10","label":"Siglec-10","symbol":"SIGLEC10","hgnc":"HGNC:15620","side":"macrophage","target":"https://onco.cc/targets/siglec10/","page":"https://onco.cc/checkpoints/immune/#siglec10","expressedOn":{"text":"Peripheral blood leukocytes: eosinophils, monocytes and an NK-cell subpopulation; an inhibitory receptor that recruits phosphatases on ligand binding.","source":{"label":"UniProt Q96LC7","url":"https://www.uniprot.org/uniprotkb/Q96LC7/entry"}},"partners":["cd24"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[],"discontinued":[]},{"id":"lilrb1","label":"LILRB1 (ILT2)","symbol":"LILRB1","hgnc":"HGNC:6605","side":"macrophage","target":"https://onco.cc/targets/lilrb1/","page":"https://onco.cc/checkpoints/immune/#lilrb1","expressedOn":{"text":"B cells, monocytes and myeloid, plasmacytoid and tolerogenic dendritic cells; decidual macrophages and NK cells (protein level).","source":{"label":"UniProt Q8NHL6","url":"https://www.uniprot.org/uniprotkb/Q8NHL6/entry"}},"partners":[],"partnerNote":{"text":"Classical and non-classical HLA class I (HLA-A, B, C, G and F); engagement protects the target cell from lysis.","source":{"label":"UniProt Q8NHL6","url":"https://www.uniprot.org/uniprotkb/Q8NHL6/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"NGM707 (anti-LILRB1/LILRB2) reached phase 1/2 with pembrolizumab; a later phase 2 study was withdrawn by the sponsor.","source":{"label":"ClinicalTrials.gov NCT04913337","url":"https://clinicaltrials.gov/study/NCT04913337"}}],"discontinued":[]},{"id":"lilrb2","label":"LILRB2 (ILT4)","symbol":"LILRB2","hgnc":"HGNC:6606","side":"macrophage","target":"https://onco.cc/targets/lilrb2/","page":"https://onco.cc/checkpoints/immune/#lilrb2","expressedOn":{"text":"Monocytes, at lower levels myeloid and plasmacytoid dendritic cells; tolerogenic IL-10-producing dendritic cells, myeloid-derived suppressor cells, B cells and low levels in NK cells.","source":{"label":"UniProt Q8N423","url":"https://www.uniprot.org/uniprotkb/Q8N423/entry"}},"partners":[],"partnerNote":{"text":"HLA class I including HLA-G; LILRB receptors negatively regulate myeloid maturation and permit a suppressive myeloid phenotype in tumours.","source":{"label":"van der Touw et al. 2017, Cancer Immunol Immunother: LILRB receptors and myeloid cells","url":"https://europepmc.org/article/MED/28638976"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"MK-4830 (anti-LILRB2) is in phase 2 with pembrolizumab, including a completed study with chemotherapy in ovarian cancer.","source":{"label":"ClinicalTrials.gov NCT05446870","url":"https://clinicaltrials.gov/study/NCT05446870"}}],"discontinued":[]}]},{"id":"costimulatory","name":"Co-stimulatory receptors and agonist targets","tone":"stimulatory","plain":"Accelerators rather than brakes. These receptors tell a T cell, or the dendritic cell that primes it, to go harder; the drugs are agonists that press them, or bispecifics that press them only where the other arm has found the tumour.","evidence":{"text":"CD40 activation licenses dendritic cells to promote antitumour T-cell activation and re-educates macrophages to destroy tumour stroma.","source":{"label":"Vonderheide 2020, Annu Rev Med: CD40 agonist antibodies in cancer immunotherapy","url":"https://europepmc.org/article/MED/31412220"}},"members":[{"id":"cd28","label":"CD28","symbol":"CD28","hgnc":"HGNC:1653","side":"immune-cell","target":"https://onco.cc/targets/cd28/","page":"https://onco.cc/checkpoints/immune/#cd28","expressedOn":{"text":"T cells and plasma cells, not less mature B cells; the receptor for CD80 and CD86 that amplifies T-cell receptor signals.","source":{"label":"UniProt P10747","url":"https://www.uniprot.org/uniprotkb/P10747/entry"}},"partners":["cd80","cd86"],"bestStatus":{"status":"phase-3","drug":"jnj-87189401"},"drugs":[{"id":"jnj-87189401","name":"JNJ-87189401","drugClass":"bispecific","status":"phase-3","note":"PSMA x CD28 co-stimulatory bispecific","page":"https://onco.cc/drugs/jnj-87189401/"}],"approvals":[],"approvedCancers":[],"trials":1,"pipelineNotes":[],"discontinued":[]},{"id":"icos","label":"ICOS","symbol":"ICOS","hgnc":"HGNC:5351","side":"immune-cell","target":"https://onco.cc/targets/icos/","page":"https://onco.cc/checkpoints/immune/#icos","expressedOn":{"text":"Activated and antigen-experienced T cells; highly expressed on tonsillar T cells in germinal centres.","source":{"label":"UniProt Q9Y6W8","url":"https://www.uniprot.org/uniprotkb/Q9Y6W8/entry"}},"partners":[],"partnerNote":{"text":"ICOS ligand (ICOSL) on antigen-presenting cells.","source":{"label":"UniProt Q9Y6W8","url":"https://www.uniprot.org/uniprotkb/Q9Y6W8/entry"}},"bestStatus":{"status":"phase-2","drug":"feladilimab"},"drugs":[{"id":"feladilimab","name":"Feladilimab","drugClass":"agonist","status":"phase-2","page":"https://onco.cc/drugs/feladilimab/"}],"approvals":[],"approvedCancers":[],"trials":2,"pipelineNotes":[],"discontinued":[{"name":"Feladilimab (INDUCE-3 and INDUCE-4, head and neck cancer)","reason":"The trial was stopped by the sponsor based on assessment of the clinical data.","source":{"label":"ClinicalTrials.gov NCT04128696","url":"https://clinicaltrials.gov/study/NCT04128696"}}]},{"id":"tnfrsf4","label":"OX40","symbol":"TNFRSF4","hgnc":"HGNC:11918","side":"immune-cell","target":"https://onco.cc/targets/tnfrsf4/","page":"https://onco.cc/checkpoints/immune/#tnfrsf4","expressedOn":{"text":"Activated T cells; OX40 ligation augments CD4 and CD8 T-cell clonal expansion, effector differentiation and survival.","source":{"label":"Croft 2009, Immunol Rev: OX40-mediated co-stimulation","url":"https://europepmc.org/article/MED/19538134"}},"partners":[],"partnerNote":{"text":"OX40 ligand (TNFSF4).","source":{"label":"UniProt P43489","url":"https://www.uniprot.org/uniprotkb/P43489/entry"}},"bestStatus":{"status":"phase-3","drug":"inbrx-106"},"drugs":[{"id":"inbrx-106","name":"INBRX-106","drugClass":"agonist","status":"phase-3","note":"hexavalent OX40 agonist","page":"https://onco.cc/drugs/inbrx-106/"}],"approvals":[],"approvedCancers":[],"trials":1,"pipelineNotes":[],"discontinued":[]},{"id":"cd137","label":"4-1BB (CD137)","symbol":"TNFRSF9","hgnc":"HGNC:11924","side":"immune-cell","target":"https://onco.cc/targets/cd137/","page":"https://onco.cc/checkpoints/immune/#cd137","expressedOn":{"text":"The surface of activated T cells; signalling enhances CD8 T-cell survival, cytotoxicity and mitochondrial activity.","source":{"label":"UniProt Q07011","url":"https://www.uniprot.org/uniprotkb/Q07011/entry"}},"partners":[],"partnerNote":{"text":"4-1BB ligand (TNFSF9).","source":{"label":"UniProt Q07011","url":"https://www.uniprot.org/uniprotkb/Q07011/entry"}},"bestStatus":{"status":"phase-3","drug":"acasunlimab"},"drugs":[{"id":"acasunlimab","name":"Acasunlimab","drugClass":"bispecific","status":"phase-3","note":"PD-L1 x 4-1BB","page":"https://onco.cc/drugs/acasunlimab/"},{"id":"utomilumab","name":"Utomilumab","drugClass":"agonist","status":"phase-3","page":"https://onco.cc/drugs/utomilumab/"},{"id":"cinrebafusp-alfa","name":"Cinrebafusp alfa","drugClass":"fusion-protein","status":"phase-2","note":"HER2 x 4-1BB anticalin","page":"https://onco.cc/drugs/cinrebafusp-alfa/"},{"id":"englumafusp-alfa","name":"Englumafusp alfa","drugClass":"fusion-protein","status":"phase-2","note":"CD19-targeted 4-1BB ligand","page":"https://onco.cc/drugs/englumafusp-alfa/"}],"approvals":[],"approvedCancers":[],"trials":5,"pipelineNotes":[],"discontinued":[{"name":"Acasunlimab (GEN1046)","reason":"Genmab decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritisation; not related to safety concerns.","source":{"label":"ClinicalTrials.gov NCT03917381","url":"https://clinicaltrials.gov/study/NCT03917381"}},{"name":"Utomilumab (PF-05082566)","reason":"Development programme terminated.","source":{"label":"ClinicalTrials.gov NCT03704298","url":"https://clinicaltrials.gov/study/NCT03704298"}}]},{"id":"tnfrsf18","label":"GITR","symbol":"TNFRSF18","hgnc":"HGNC:11914","side":"immune-cell","target":"https://onco.cc/targets/tnfrsf18/","page":"https://onco.cc/checkpoints/immune/#tnfrsf18","expressedOn":{"text":"Lymph node and peripheral blood leukocytes, weakly in spleen.","source":{"label":"UniProt Q9Y5U5","url":"https://www.uniprot.org/uniprotkb/Q9Y5U5/entry"}},"partners":[],"partnerNote":{"text":"GITR ligand (TNFSF18).","source":{"label":"UniProt Q9Y5U5","url":"https://www.uniprot.org/uniprotkb/Q9Y5U5/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"BMS-986156 (GITR agonist) completed phase 1/2 alone and with nivolumab.","source":{"label":"ClinicalTrials.gov NCT02598960","url":"https://clinicaltrials.gov/study/NCT02598960"}}],"discontinued":[{"name":"TRX518 (GITR agonist)","reason":"Product development discontinued unrelated to safety.","source":{"label":"ClinicalTrials.gov NCT03861403","url":"https://clinicaltrials.gov/study/NCT03861403"}}]},{"id":"cd27","label":"CD27","symbol":"CD27","hgnc":"HGNC:11922","side":"immune-cell","target":"https://onco.cc/targets/cd27/","page":"https://onco.cc/checkpoints/immune/#cd27","expressedOn":{"text":"Most T lymphocytes, also NK and B cells; a co-stimulatory receptor activated by CD70 on B cells.","source":{"label":"UniProt P26842","url":"https://www.uniprot.org/uniprotkb/P26842/entry"}},"partners":[],"partnerNote":{"text":"CD70, which has its own target page.","source":{"label":"UniProt P26842","url":"https://www.uniprot.org/uniprotkb/P26842/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"Varlilumab (CD27 agonist) reached phase 2 with nivolumab in aggressive B-cell lymphoma.","source":{"label":"ClinicalTrials.gov NCT03038672","url":"https://clinicaltrials.gov/study/NCT03038672"}}],"discontinued":[{"name":"Varlilumab combination studies","reason":"Portfolio re-prioritisation.","source":{"label":"ClinicalTrials.gov NCT02386111","url":"https://clinicaltrials.gov/study/NCT02386111"}}]},{"id":"cd40","label":"CD40","symbol":"CD40","hgnc":"HGNC:11919","side":"tumour-or-apc","target":"https://onco.cc/targets/cd40/","page":"https://onco.cc/checkpoints/immune/#cd40","expressedOn":{"text":"B cells and primary carcinomas (UniProt); agonists license dendritic cells and re-educate macrophages.","source":{"label":"Vonderheide 2020, Annu Rev Med: CD40 agonist antibodies in cancer immunotherapy","url":"https://europepmc.org/article/MED/31412220"}},"partners":[],"partnerNote":{"text":"CD40 ligand (CD40LG, CD154) on activated T cells.","source":{"label":"UniProt P25942","url":"https://www.uniprot.org/uniprotkb/P25942/entry"}},"bestStatus":{"status":"phase-2","drug":"selicrelumab"},"drugs":[{"id":"selicrelumab","name":"Selicrelumab","drugClass":"agonist","status":"phase-2","page":"https://onco.cc/drugs/selicrelumab/"},{"id":"mitazalimab","name":"Mitazalimab","drugClass":"agonist","status":"phase-2","page":"https://onco.cc/drugs/mitazalimab/"}],"approvals":[],"approvedCancers":[],"trials":2,"pipelineNotes":[],"discontinued":[{"name":"Selicrelumab (intratumoural, with atezolizumab)","reason":"End of drug development.","source":{"label":"ClinicalTrials.gov NCT03892525","url":"https://clinicaltrials.gov/study/NCT03892525"}}]}]},{"id":"metabolic","name":"Metabolic checkpoints","tone":"metabolic","plain":"Enzymes and receptors that change the chemistry around the tumour: they use up tryptophan or turn spilt ATP into adenosine, and either change starves or sedates T cells.","evidence":{"text":"CD39 and CD73 are cell-surface enzymes that catabolise extracellular ATP into adenosine; ectonucleotidases and adenosine receptors have emerged as therapeutic targets.","source":{"label":"Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis","url":"https://europepmc.org/article/MED/29758241"}},"members":[{"id":"ido1","label":"IDO1","symbol":"IDO1","hgnc":"HGNC:6059","side":"intracellular","target":"https://onco.cc/targets/ido1/","page":"https://onco.cc/checkpoints/immune/#ido1","expressedOn":{"text":"Mature dendritic cells in lymphoid organs, some epithelial cells of the female genital tract, endothelial cells of term placenta and lung parenchyma; weak in most normal tissues but inducible.","source":{"label":"UniProt P14902","url":"https://www.uniprot.org/uniprotkb/P14902/entry"}},"partners":[],"partnerNote":{"text":"Converts tryptophan to kynurenine, which activates the aryl hydrocarbon receptor and yields tolerant dendritic cells and regulatory T cells.","source":{"label":"Cheong and Sun 2018, Trends Pharmacol Sci: the IDO1/TDO2-kynurenine-AhR pathway","url":"https://europepmc.org/article/MED/29254698"}},"bestStatus":{"status":"phase-3","drug":"io102-io103"},"drugs":[{"id":"epacadostat","name":"Epacadostat","drugClass":"small-molecule","status":"negative","page":"https://onco.cc/drugs/epacadostat/"},{"id":"io102-io103","name":"IO102-IO103","drugClass":"vaccine","status":"phase-3","page":"https://onco.cc/drugs/io102-io103/"}],"approvals":[],"approvedCancers":[],"trials":5,"pipelineNotes":[],"discontinued":[{"name":"Epacadostat programme after ECHO-301","reason":"Terminated due to emergent data from another study and unrelated to safety (registry text on a companion Incyte study).","source":{"label":"ClinicalTrials.gov NCT03277352","url":"https://clinicaltrials.gov/study/NCT03277352"}}]},{"id":"tdo2","label":"TDO2","symbol":"TDO2","hgnc":"HGNC:11708","side":"intracellular","target":"https://onco.cc/targets/tdo2/","page":"https://onco.cc/checkpoints/immune/#tdo2","expressedOn":{"text":"Catalyses the same tryptophan-to-kynurenine commitment step as IDO1; the cited review treats IDO1 and TDO2 together as drivers of tumour immune escape. UniProt gives no tissue distribution.","source":{"label":"Cheong and Sun 2018, Trends Pharmacol Sci: the IDO1/TDO2-kynurenine-AhR pathway","url":"https://europepmc.org/article/MED/29254698"}},"partners":[],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"No TDO2-selective agent was found in ClinicalTrials.gov under the drug names the corpus knows; the LY3381916 study is an IDO1 programme and was terminated for business reasons.","source":{"label":"ClinicalTrials.gov NCT03343613","url":"https://clinicaltrials.gov/study/NCT03343613"}}],"discontinued":[]},{"id":"cd73-adenosine","label":"CD73","symbol":"NT5E","hgnc":"HGNC:8021","side":"tumour-or-apc","target":"https://onco.cc/targets/cd73-adenosine/","page":"https://onco.cc/checkpoints/immune/#cd73-adenosine","expressedOn":{"text":"Broadly expressed; the ectonucleotidase that finishes the breakdown of extracellular ATP into adenosine.","source":{"label":"Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis","url":"https://europepmc.org/article/MED/29758241"}},"partners":["entpd1","adora2a"],"bestStatus":{"status":"phase-3","drug":"oleclumab"},"drugs":[{"id":"oleclumab","name":"Oleclumab","drugClass":"antibody","status":"phase-3","page":"https://onco.cc/drugs/oleclumab/"},{"id":"quemliclustat","name":"Quemliclustat","drugClass":"small-molecule","status":"phase-3","page":"https://onco.cc/drugs/quemliclustat/"},{"id":"ak119","name":"AK119","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/ak119/"},{"id":"mavrostobart","name":"Mavrostobart","drugClass":"antibody","status":"phase-2","page":"https://onco.cc/drugs/mavrostobart/"}],"approvals":[],"approvedCancers":[],"trials":13,"pipelineNotes":[],"discontinued":[{"name":"Oleclumab plus durvalumab doublet (platform arms)","reason":"Overall clinical activity (ORR) for oleclumab plus durvalumab is minimal across tumour types and does not support further evaluation of this doublet.","source":{"label":"ClinicalTrials.gov NCT04262388","url":"https://clinicaltrials.gov/study/NCT04262388"}}]},{"id":"entpd1","label":"CD39","symbol":"ENTPD1","hgnc":"HGNC:3363","side":"tumour-or-apc","target":"https://onco.cc/targets/entpd1/","page":"https://onco.cc/checkpoints/immune/#entpd1","expressedOn":{"text":"Primarily activated lymphoid cells; also endothelium, and highly in placenta, lung, skeletal muscle and kidney.","source":{"label":"UniProt P49961","url":"https://www.uniprot.org/uniprotkb/P49961/entry"}},"partners":["cd73-adenosine"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"TTX-030 (anti-CD39) completed a phase 2 study with chemotherapy, with or without budigalimab, in first-line metastatic pancreatic cancer.","source":{"label":"ClinicalTrials.gov NCT06119217","url":"https://clinicaltrials.gov/study/NCT06119217"}}],"discontinued":[]},{"id":"adora2a","label":"Adenosine A2A receptor","symbol":"ADORA2A","hgnc":"HGNC:263","side":"immune-cell","target":"https://onco.cc/targets/adora2a/","page":"https://onco.cc/checkpoints/immune/#adora2a","expressedOn":{"text":"Broadly expressed adenosine receptor; G-protein coupled, raising cyclic AMP in the cells that carry it.","source":{"label":"Allard et al. 2019, Immunol Rev: targeting the CD73-adenosine axis","url":"https://europepmc.org/article/MED/29758241"}},"partners":["cd73-adenosine"],"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"Ciforadenant (A2A antagonist) is in phase 1b/2 with ipilimumab and nivolumab.","source":{"label":"ClinicalTrials.gov NCT05501054","url":"https://clinicaltrials.gov/study/NCT05501054"}},{"text":"Etrumadenant (A2A/A2B antagonist) is in phase 2 combinations in pancreatic cancer.","source":{"label":"ClinicalTrials.gov NCT06048484","url":"https://clinicaltrials.gov/study/NCT06048484"}},{"text":"Inupadenant (A2A antagonist) is in phase 2 with chemotherapy in non-squamous non-small-cell lung cancer.","source":{"label":"ClinicalTrials.gov NCT05403385","url":"https://clinicaltrials.gov/study/NCT05403385"}}],"discontinued":[]}]},{"id":"b7-family","name":"Other B7 family members","tone":"ligand","plain":"Relatives of PD-L1 and CD80 whose receptors are only partly known. Because tumours over-express them, most drugs treat them as an address for an antibody-drug conjugate rather than as a brake to release.","evidence":{"text":"B7-H3, B7x (B7-H4) and HHLA2 form the third phylogenetic group of the B7-CD28 family, with antagonistic antibodies and agonistic fusion proteins emerging for cancer.","source":{"label":"Janakiram et al. 2017, Immunol Rev: the third group of the B7-CD28 family","url":"https://europepmc.org/article/MED/28258693"}},"members":[{"id":"b7h3","label":"B7-H3 (CD276)","symbol":"CD276","hgnc":"HGNC:19137","side":"tumour-or-apc","target":"https://onco.cc/targets/b7h3/","page":"https://onco.cc/checkpoints/immune/#b7h3","expressedOn":{"text":"Ubiquitous transcript but not detectable on peripheral blood lymphocytes or granulocytes; weak on resting monocytes, present on monocyte-derived dendritic cells and sinonasal epithelium.","source":{"label":"UniProt Q5ZPR3","url":"https://www.uniprot.org/uniprotkb/Q5ZPR3/entry"}},"partners":[],"partnerNote":{"text":"Receptor not established; the protein may inhibit NK-mediated lysis of tumour cells.","source":{"label":"UniProt Q5ZPR3","url":"https://www.uniprot.org/uniprotkb/Q5ZPR3/entry"}},"bestStatus":{"status":"phase-3","drug":"ifinatamab-deruxtecan"},"drugs":[{"id":"ifinatamab-deruxtecan","name":"Ifinatamab deruxtecan","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/ifinatamab-deruxtecan/"},{"id":"yl201","name":"YL201","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/yl201/"},{"id":"qlc5508","name":"QLC5508","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/qlc5508/"},{"id":"bnt324","name":"BNT324","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/bnt324/"},{"id":"hs-20093","name":"HS-20093","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/hs-20093/"},{"id":"bcb-276","name":"BCB-276","drugClass":"cell-therapy","status":"phase-2","page":"https://onco.cc/drugs/bcb-276/"}],"approvals":[],"approvedCancers":[],"trials":40,"pipelineNotes":[],"discontinued":[]},{"id":"b7h4","label":"B7-H4 (VTCN1)","symbol":"VTCN1","hgnc":"HGNC:28873","side":"tumour-or-apc","target":"https://onco.cc/targets/b7h4/","page":"https://onco.cc/checkpoints/immune/#b7h4","expressedOn":{"text":"Over-expressed in breast, ovarian, endometrial, renal cell and non-small-cell lung cancers; on activated T and B cells, monocytes and dendritic cells but not most normal tissues (protein level).","source":{"label":"UniProt Q7Z7D3","url":"https://www.uniprot.org/uniprotkb/Q7Z7D3/entry"}},"partners":[],"bestStatus":{"status":"phase-3","drug":"hs-20089"},"drugs":[{"id":"puxitatug-samrotecan","name":"Puxitatug samrotecan","drugClass":"adc","status":"phase-2","page":"https://onco.cc/drugs/puxitatug-samrotecan/"},{"id":"hs-20089","name":"HS-20089","drugClass":"adc","status":"phase-3","page":"https://onco.cc/drugs/hs-20089/"}],"approvals":[],"approvedCancers":[],"trials":4,"pipelineNotes":[],"discontinued":[]},{"id":"hhla2","label":"HHLA2 (B7-H7)","symbol":"HHLA2","hgnc":"HGNC:4905","side":"tumour-or-apc","target":"https://onco.cc/targets/hhla2/","page":"https://onco.cc/checkpoints/immune/#hhla2","expressedOn":{"text":"High in colon, kidney, testis, lung and pancreas; among immune cells, B cells, dendritic cells and macrophages, not T cells.","source":{"label":"UniProt Q9UM44","url":"https://www.uniprot.org/uniprotkb/Q9UM44/entry"}},"partners":[],"partnerNote":{"text":"TMIGD2 (CD28H), through which it co-stimulates T cells.","source":{"label":"UniProt Q9UM44","url":"https://www.uniprot.org/uniprotkb/Q9UM44/entry"}},"bestStatus":null,"drugs":[],"approvals":[],"approvedCancers":[],"trials":0,"pipelineNotes":[{"text":"No HHLA2-directed agent is in the corpus, and none was looked up in the registry for this map; the family review lists antagonistic antibodies and agonistic fusion proteins as emerging.","source":{"label":"Janakiram et al. 2017, Immunol Rev: the third group of the B7-CD28 family","url":"https://europepmc.org/article/MED/28258693"}}],"discontinued":[]}]},{"id":"soluble","name":"Soluble brakes of the microenvironment","tone":"soluble","plain":"Not receptors but secreted signals that quieten immune cells across a whole tumour. The cited review frames them as immunosuppressive cytokines rather than checkpoints in the strict sense; they are listed here because the drugs against TGF-beta are fused to checkpoint antibodies.","evidence":{"text":"HPV up-regulates IL-10 and TGF-beta1 to produce a local immunosuppressive environment that inhibits the antitumour immune response.","source":{"label":"Torres-Poveda et al. 2014, Infect Agent Cancer: IL-10 and TGF-beta1 in local immunosuppression","url":"https://europepmc.org/article/MED/25302175"}},"members":[{"id":"tgfb1","label":"TGF-beta 1","symbol":"TGFB1","hgnc":"HGNC:11766","side":"soluble","target":"https://onco.cc/targets/tgfb1/","page":"https://onco.cc/checkpoints/immune/#tgfb1","expressedOn":{"text":"Stored latent in the extracellular matrix; highly expressed in bone and articular cartilage (UniProt). Up-regulated with IL-10 in HPV-driven cervical lesions to form a local immunosuppressive environment.","source":{"label":"Torres-Poveda et al. 2014, Infect Agent Cancer: IL-10 and TGF-beta1 in local immunosuppression","url":"https://europepmc.org/article/MED/25302175"}},"partners":[],"partnerNote":{"text":"TGF-beta receptors I and II; the drugs in the corpus are receptor-domain traps fused to a PD-L1 or EGFR antibody, or antisense against TGF-beta 2.","source":{"label":"UniProt P01137","url":"https://www.uniprot.org/uniprotkb/P01137/entry"}},"bestStatus":{"status":"phase-3","drug":"retlirafusp-alfa"},"drugs":[{"id":"retlirafusp-alfa","name":"Retlirafusp alfa","drugClass":"fusion-protein","status":"phase-3","note":"PD-L1 x TGF-beta trap","page":"https://onco.cc/drugs/retlirafusp-alfa/"},{"id":"ficerafusp-alfa","name":"Ficerafusp alfa","drugClass":"fusion-protein","status":"phase-3","note":"EGFR x TGF-beta trap","page":"https://onco.cc/drugs/ficerafusp-alfa/"},{"id":"trabedersen","name":"Trabedersen","drugClass":"antisense","status":"phase-3","note":"TGF-beta 2 antisense","page":"https://onco.cc/drugs/trabedersen/"}],"approvals":[],"approvedCancers":[],"trials":8,"pipelineNotes":[],"discontinued":[{"name":"Bintrafusp alfa (PD-L1 x TGF-beta trap) in biliary tract cancer","reason":"Discontinued as it was unlikely to meet the primary endpoint of overall survival (registry text on the neoadjuvant companion study).","source":{"label":"ClinicalTrials.gov NCT04727541","url":"https://clinicaltrials.gov/study/NCT04727541"}},{"name":"Bintrafusp alfa programme","reason":"The sponsor decided to no longer develop the drug and stop support of studies using the drug.","source":{"label":"ClinicalTrials.gov NCT04220775","url":"https://clinicaltrials.gov/study/NCT04220775"}}]},{"id":"il10","label":"IL-10","symbol":"IL10","hgnc":"HGNC:5962","side":"soluble","target":"https://onco.cc/targets/il10/","page":"https://onco.cc/checkpoints/immune/#il10","expressedOn":{"text":"Produced by T cells, macrophages, mast cells and other cell types; a major anti-inflammatory cytokine signalling through IL10RA/IL10RB to STAT3.","source":{"label":"UniProt P22301","url":"https://www.uniprot.org/uniprotkb/P22301/entry"}},"partners":[],"partnerNote":{"text":"The clinical programme ran the other way: pegylated IL-10 was given to stimulate CD8 T cells, and the corpus's LB4330 delivers IL-10 to Claudin 18.2-positive tumours.","source":{"label":"ClinicalTrials.gov NCT02923921","url":"https://clinicaltrials.gov/study/NCT02923921"}},"bestStatus":{"status":"phase-2","drug":"lb4330"},"drugs":[{"id":"lb4330","name":"LB4330","drugClass":"fusion-protein","status":"phase-2","note":"Claudin 18.2 x IL-10 fusion, an agonist","page":"https://onco.cc/drugs/lb4330/"}],"approvals":[],"approvedCancers":[],"trials":1,"pipelineNotes":[],"discontinued":[{"name":"Pegilodecakin (pegylated IL-10) with PD-1 blockade (CYPRESS-1 and CYPRESS-2)","reason":"Closed early after the planned primary analysis because the risk-benefit ratio is unfavourable.","source":{"label":"ClinicalTrials.gov NCT03382899","url":"https://clinicaltrials.gov/study/NCT03382899"}}]}]}]}