4-1BB | Tumour necrosis factor (TNF) receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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4-1BB

  Target has curated data in GtoImmuPdb

Target id: 1878

Nomenclature: 4-1BB

Systematic Nomenclature: TNFRSF9

Family: Tumour necrosis factor (TNF) receptor family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 254 19p13.3 TNFRSF9 TNF receptor superfamily member 9
Mouse 1 309 17 D Tnfrsf9 tumor necrosis factor receptor superfamily
Rat 1 308 9 Tnfrsf9 TNF receptor superfamily member 9
Previous and Unofficial Names
ILA | CD137 | Ly63 | tumor necrosis factor receptor superfamily, member 9 | tumor necrosis factor receptor superfamily
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Adaptor proteins (Human)
TRAF1, TRAF2, TRAF3

Download all structure-activity data for this target as a CSV file

Antibodies
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Antibody Sp. Action Affinity Parameter Reference
utomilumab Hs Agonist 8.1 pKd 2
pKd 8.1 (Kd 8.7x10-9 M) [2]
Description: Binding to 4-1BB extracellular domain measured using a surface plasmon resonance (SPR) biosensor assay.
urelumab Hs Agonist 7.8 pKd 3
pKd 7.8 (Kd 1.661x10-8 M) [3]
Description: Dissociation constant for the 20H4-9-IgG4 clone binding to human 4-1BB
Antibody Comments
Pfizer are developing utomilumab (PF-05082566) as a novel immuno-oncology biologic.
Bristol Meyers Squibb are developing urelumab (BMS-663513) for its potential immunostimulatory and antineoplastic activities.
Alligator Bioscience have their agonistic anti-4-1BB monoclonal, ATOR-1017 in preclinical development. ATOR-1017 is likely the subject of patent WO2018091740A2 [1]. It is an IgG4 antibody with enhanced ability to cross-link to Fc-γ receptors on immune cells, and therefore has a high tumour killing capacity.
Immunopharmacology Comments
4-1BB is a costimulatory receptor that is highly expressed on both T cells and NK cells in the tumour environment. Since activation of 4-1BB produces an immunostimulatory effect that supports the immune cells involved in tumour control it is a target for immuno-oncology drug development. Targeting 4-1BB using monoclonal antibodies that act as agonists produces an immunostimulatory effect that enhances T-cell function and promotes anti-tumour activity [2]. For example, agonist antibody utomilumab is reported to enhance T cell function and promote anti-tumour action in cancer xenograft models [2], and both utomilumab and urelumab have advanced to clinical trial.
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 4 GO processes
GO:0005031 tumor necrosis factor-activated receptor activity IBA
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS
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GO:2001180 negative regulation of interleukin-10 secretion IEA
GO:2001183 negative regulation of interleukin-12 secretion IEA
General Comments
4-1BB (CD137, TNFRSF9) is a costimulatory receptor expressed on T cells, ligand activation of which under normal circumstances stimulates cellular proliferation, survival, and cytokine production.

References

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1. Ellmark P, Fritzell S, Furebring C, Petersson J, Säll A, Smith KE, Varas L, Von SL, Veitonmäki N. (2018) Novel antibodies and uses thereof. Patent number: WO2018091740A2. Assignee: Alligator Bioscience Ab. Priority date: 21/11/2016. Publication date: 24/05/2018.

2. Fisher TS, Kamperschroer C, Oliphant T, Love VA, Lira PD, Doyonnas R, Bergqvist S, Baxi SM, Rohner A, Shen AC et al.. (2012) Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol. Immunother., 61 (10): 1721-33. [PMID:22406983]

3. Jure-Kunkel, M, Hefta LJ, Santoro M, Ganguly S, Halk EL. (2005) Fully human antibodies against human 4-1bb (cd137). Patent number: WO2005035584. Assignee: Bristol-Myers Squibb Company. Priority date: 10/10/2003. Publication date: 21/04/2005.

Contributors

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How to cite this page

David MacEwan.
Tumour necrosis factor (TNF) receptor family: 4-1BB. Last modified on 21/06/2018. Accessed on 16/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1878.