{"slug":"checkpoint-map","tag":"checkpoint-map","variants":["checkpoint-map"],"description":"No description yet","count":26,"kinds":{"target":26},"related":[],"records":[{"id":"btla","kind":"target","name":"BTLA","route":"/targets/btla/","tldr":"BTLA is a brake on T and B cells that is pressed by HVEM, a molecule many tumours carry. An antibody that blocks it is being tested with PD-1 blockade in small-cell lung cancer."},{"id":"klrc1","kind":"target","name":"NKG2A (KLRC1)","route":"/targets/klrc1/","tldr":"NKG2A is the brake on NK cells and some killer T cells that is pressed by HLA-E, a molecule tumours raise to look like self. Monalizumab blocks it and is in phase 3 with durvalumab in lung cancer and with cetuximab in head and neck cancer."},{"id":"kir2dl1","kind":"target","name":"KIR2DL1 (inhibitory KIR)","route":"/targets/kir2dl1/","tldr":"Inhibitory KIRs are the receptors NK cells use to recognise a person's own HLA-C and stand down. Lirilumab, an antibody that blocks three of them, reached phase 2 but was dropped for blood cancers."},{"id":"cd96","kind":"target","name":"CD96","route":"/targets/cd96/","tldr":"CD96 sits on T and NK cells and binds CD155, the same molecule TIGIT reads on tumour cells. It is the least tested of that family; one blocking antibody is in phase 2 platform trials in lung cancer."},{"id":"pvrig","kind":"target","name":"PVRIG (CD112R)","route":"/targets/pvrig/","tldr":"PVRIG is a brake on killer T cells and NK cells that reads CD112 on tumour cells, a cousin of the TIGIT pair. The antibody COM701 blocks it and is being tested in ovarian cancer."},{"id":"cd86","kind":"target","name":"CD86 (B7-2)","route":"/targets/cd86/","tldr":"CD86 is one of the two B7 molecules on antigen-presenting cells that either wake a T cell up (through CD28) or calm it down (through CTLA-4). Ipilimumab works by stopping CTLA-4 from hogging CD86 and CD80."},{"id":"fgl1","kind":"target","name":"FGL1","route":"/targets/fgl1/","tldr":"FGL1 is a liver protein that some tumours secrete; it binds LAG-3 on T cells and switches them off, separately from the MHC class II route. It explains part of how LAG-3 blockade works."},{"id":"lgals9","kind":"target","name":"Galectin-9 (LGALS9)","route":"/targets/lgals9/","tldr":"Galectin-9 is a sugar-binding protein that presses TIM-3 on T cells and can kill the helper T cells that carry it. Tumour blood vessels make more of it than normal ones."},{"id":"pvr","kind":"target","name":"CD155 (PVR)","route":"/targets/pvr/","tldr":"CD155 is the molecule on tumour cells that TIGIT and CD96 read; normal tissue barely shows it, many tumours show a lot. Every TIGIT antibody works by breaking the CD155 handshake."},{"id":"nectin2","kind":"target","name":"CD112 (nectin-2)","route":"/targets/nectin2/","tldr":"CD112 is a widespread cell-adhesion molecule that can either encourage a T cell (through CD226) or hold it back (through PVRIG and TIGIT), depending on which receptor grabs it first."},{"id":"hla-e","kind":"target","name":"HLA-E","route":"/targets/hla-e/","tldr":"HLA-E is the self badge that NKG2A on NK cells reads. Tumours raise it to escape NK cells; monalizumab blocks the reader rather than the badge."},{"id":"cd24","kind":"target","name":"CD24","route":"/targets/cd24/","tldr":"CD24 is a second 'don't eat me' badge after CD47: tumours show it to Siglec-10 on macrophages, which then leave them alone. Blocking antibodies are in first-in-human trials."},{"id":"siglec10","kind":"target","name":"Siglec-10","route":"/targets/siglec10/","tldr":"Siglec-10 is the receptor on macrophages and other blood cells that reads the CD24 'don't eat me' badge on tumour cells and calls off the attack."},{"id":"lilrb1","kind":"target","name":"LILRB1 (ILT2)","route":"/targets/lilrb1/","tldr":"LILRB1 is a brake on macrophages, dendritic cells and some NK and T cells that reads ordinary HLA class I, so any cell showing HLA is protected. Antibodies that block it, with or without LILRB2, are in early trials."},{"id":"lilrb2","kind":"target","name":"LILRB2 (ILT4)","route":"/targets/lilrb2/","tldr":"LILRB2 is a brake on monocytes and dendritic cells that reads HLA-G and other HLA class I molecules and keeps them in a tolerant, tumour-friendly state. The antibody MK-4830 blocks it and is in phase 2 with pembrolizumab."},{"id":"tnfrsf4","kind":"target","name":"OX40 (TNFRSF4)","route":"/targets/tnfrsf4/","tldr":"OX40 is an accelerator that appears on T cells once they are switched on; pressing it makes them multiply and survive longer. Agonist antibodies against it are in trials, including a phase 3 in head and neck cancer."},{"id":"tnfrsf18","kind":"target","name":"GITR (TNFRSF18)","route":"/targets/tnfrsf18/","tldr":"GITR is an accelerator on T cells that agonist antibodies tried to press to boost immunotherapy. Several reached early trials; one programme was dropped for reasons unrelated to safety."},{"id":"cd27","kind":"target","name":"CD27","route":"/targets/cd27/","tldr":"CD27 is an accelerator on most T cells that is pressed by CD70. Agonist antibodies against it reached phase 2 in lymphoma; its partner CD70 is a separate target for antibodies and CAR-T cells."},{"id":"cd40","kind":"target","name":"CD40","route":"/targets/cd40/","tldr":"CD40 sits on the cells that teach T cells what to attack. Agonist antibodies press it to turn cold tumours hot; the strongest signals so far are in pancreatic cancer with chemotherapy."},{"id":"tdo2","kind":"target","name":"TDO2","route":"/targets/tdo2/","tldr":"TDO2 does the same job as IDO1, breaking down tryptophan into kynurenine, which quietens T cells. It is one reason IDO1 inhibitors alone may not have been enough; no TDO2 drug has reached late trials."},{"id":"entpd1","kind":"target","name":"CD39 (ENTPD1)","route":"/targets/entpd1/","tldr":"CD39 is the first of two enzymes that turn the ATP spilt by dying tumour cells into adenosine, which sedates T cells. Blocking it keeps the ATP alarm ringing; one antibody has completed phase 2 in pancreatic cancer."},{"id":"adora2a","kind":"target","name":"Adenosine A2A receptor (ADORA2A)","route":"/targets/adora2a/","tldr":"The A2A receptor is where adenosine lands on a T cell and tells it to rest. Oral antagonists, cousins of caffeine, are in phase 2 combinations with PD-1 blockade and chemotherapy."},{"id":"hhla2","kind":"target","name":"HHLA2 (B7-H7)","route":"/targets/hhla2/","tldr":"HHLA2 is a B7 relative found on gut, kidney and lung tissue and on many tumours; it can both encourage and restrain T cells depending on the receptor. No drug against it is in the corpus yet."},{"id":"il10","kind":"target","name":"Interleukin-10 (IL10)","route":"/targets/il10/","tldr":"IL-10 is a calming signal that many immune cells release; tumours and the viruses behind them raise it to keep the immune system quiet. Oddly, the main cancer drug built on it gave more IL-10 rather than less, and failed."},{"id":"bub1","kind":"target","name":"BUB1","route":"/targets/bub1/","tldr":"BUB1 is one of the kinases that stops a dividing cell pulling its chromosomes apart before every one is attached. Inhibitors exist in the laboratory; none has reached patients."},{"id":"ttk","kind":"target","name":"MPS1 (TTK)","route":"/targets/ttk/","tldr":"MPS1 arms the checkpoint that holds a dividing cell until its chromosomes are attached. Blocking it lets cancer cells divide carelessly and die; one inhibitor is in phase 1/2 in breast cancer."}]}