CD137 (4-1BB, TNFRSF9)
4-1BB is a switch on activated T cells that makes them live longer and kill better. Rather than press it everywhere, new bispecific antibodies press it only on T cells that are already touching a tumour cell marked by PD-L1 or HER2.
Overview
TNFRSF9 (chromosome 1p36.23) encodes CD137 (4-1BB), the receptor for 4-1BB ligand (TNFSF9); its signal enhances CD8 T-cell survival, cytotoxicity and mitochondrial activity and so promotes immunity against viruses and tumours (UniProt Q07011). In OnCo it is the costimulatory arm of two tumour-anchored bispecifics: acasunlimab (PD-L1 x 4-1BB) in phase 3 for NSCLC, and cinrebafusp alfa (PRS-343), a HER2/4-1BB anticalin-antibody fusion protein that binds HER2 on tumour cells while engaging 4-1BB to costimulate T cells, in HER2-positive gastric cancer.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · 4-1BB is a switch on activated T cells that makes them live longer and kill better. Rather than press it everywhere, new bispecific antibodies press it only on T cells that are already touching a tumour cell marked by PD-L1 or HER2.
- 1 · What it is
4-1BB is a switch on activated T cells that makes them live longer and kill better. Rather than press it everywhere, new bispecific antibodies press it only on T cells that are already touching a tumour cell marked by PD-L1 or HER2.
- 2 · What goes wrong in cancer
Both corpus agents cluster 4-1BB only where the other arm has bound a tumour antigen (PD-L1 or HER2), so costimulation is confined to T cells in contact with the tumour rather than delivered systemically.
- 3 · How drugs use it
2 products aim at CD137 (4-1BB, TNFRSF9): bispecific antibodies and other agents. Because it sits on the outside of the cell, it can be reached from the bloodstream: antibodies flag the cell, ADCs deliver a toxin, radioligands deliver radiation, and CAR-T or bispecifics bring a T cell.
External identifiers
Biology
Both corpus agents cluster 4-1BB only where the other arm has bound a tumour antigen (PD-L1 or HER2), so costimulation is confined to T cells in contact with the tumour rather than delivered systemically.
- Activated CD8 T cells
- NSCLC (acasunlimab) and HER2-positive gastric cancer (cinrebafusp alfa) trials
Acasunlimab is an experimental bispecific antibody from Genmab in phase 3 trials for non-small-cell lung cancer, aimed at PD-L1.
Cinrebafusp alfa is an experimental fusion protein from Pieris Pharmaceuticals in phase 2 trials for gastric & gastro-oesophageal junction cancer, aimed at HER2.
Notes
top- Prevalence not recorded in this wave: HGNC and UniProt carry no positivity rates and no other source was consulted.
Latest papers
topQuery for this target: (TITLE:"CD137" OR ABSTRACT:"CD137" OR TITLE:"4-1BB, TNFRSF9" OR ABSTRACT:"4-1BB, TNFRSF9" OR TITLE:"TNFRSF9" OR ABSTRACT:"TNFRSF9" OR TITLE:"4-1BB" OR ABSTRACT:"4-1BB" OR TITLE:"ILA" OR ABSTRACT:"ILA" OR TITLE:"TNF receptor superfamily member 9" OR ABSTRACT:"TNF receptor superfamily member 9") 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 CD137 (4-1BB, TNFRSF9), not a curated reading list.
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