Top ▲

OX40

Click here for help

Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1873

Nomenclature: OX40

Systematic Nomenclature: TNFRSF4

Family: Tumour necrosis factor (TNF) receptor family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 277 1p36.33 TNFRSF4 TNF receptor superfamily member 4
Mouse 1 272 4 87.68 cM Tnfrsf4 tumor necrosis factor receptor superfamily, member 4
Rat 1 271 5q36 Tnfrsf4 TNF receptor superfamily member 4
Previous and Unofficial Names Click here for help
ACT35 | CD134 | TXGP1L | MRC OX40 | OX40L receptor | Tax-transcriptionally activated glycoprotein 1 | tumor necrosis factor (ligand) superfamily, member 4 | tumor necrosis factor receptor superfamily
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
OX-40 ligand {Sp: Human}
Adaptor proteins (Human)
TRAF1, TRAF2, TRAF3, TRAF5

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
vonlerolizumab Peptide Primary target of this compound Hs Agonist - - 5
[5]
Antibody Comments
The anti-OX40 monoclonal antibodies (mAbs) GSK3174998, BMS-986178 [4] and MEDI6469 [2] are examples that are in active clinical development (as of Feb. 2021) as potential immuno-oncology agents [1]. Blocking OX40 signalling is predicted to enhance anti-tumour T cell immunity.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1 [PMID: 24930776] Small molecule or natural product Immunopharmacology Ligand Hs Binding 5.9 pIC50 8
pIC50 5.9 (IC50 1.2x10-6 M) [8]
Immunopharmacology Comments
The OX40/OX40L pair is involved in late T-cell costimulatory signalling and both are transiently expressed following antigen recognition. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [9]. Amgen and Kyowa Kirin are partnering on the latter's anti-OX40 antibody KHK4083, for moderate to severe atopic dermatitis [6]. If successful this partnership could pursue KHK4083's potential in other inflammatory diseases [3,7].
Anti-OX40 mAbs are also being investigated for neoadjuvant activity, as a mechanism to enhance anti-tumour T cell activity in cancer patients [2].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IBA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0042098 T cell proliferation ISS
GO:0070236 negative regulation of activation-induced cell death of T cells IBA
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes
GO:0030890 positive regulation of B cell proliferation ISS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0030890 positive regulation of B cell proliferation ISS
GO:0070236 negative regulation of activation-induced cell death of T cells IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0005031 tumor necrosis factor-activated receptor activity IBA
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0030890 positive regulation of B cell proliferation ISS
GO:0042098 T cell proliferation ISS
Immuno Process:  Barrier integrity
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0001618 virus receptor activity IEA

References

Show »

1. Cebada J, Perez-Santos M, Bandala C, Lara-Padilla E, Herrera-Camacho I, Rosas-Murrieta NH, Millán-Pérez Peña L, Monjaraz E, Flores A, Anaya-Ruiz M. (2021) OX40 agonists for cancer treatment: a patent review. Expert Opin Ther Pat, 31 (1): 81-90. [PMID:32945223]

2. Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang SC, Koguchi Y, Bifulco CB, Bernard B, Leidner RS et al.. (2021) Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun, 12 (1): 1047. [PMID:33594075]

3. Furihata K, Ishiguro Y, Yoshimura N, Ito H, Katsushima S, Kaneko E, Shimabe M, Mukai M, Watanabe R, Morishige T. (2021) A Phase 1 Study of KHK4083: A Single-Blind, Randomized, Placebo-Controlled Single-Ascending-Dose Study in Healthy Adults and an Open-Label Multiple-Dose Study in Patients With Ulcerative Colitis. Clin Pharmacol Drug Dev, [Epub ahead of print]. DOI: 10.1002/cpdd.918 [PMID:33512065]

4. Gutierrez M, Moreno V, Heinhuis KM, Olszanski AJ, Spreafico A, Ong M, Chu Q, Carvajal RD, Trigo J, De Olza MO et al.. (2021) OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Clin Cancer Res, 27 (2): 460-472. [PMID:33148673]

5. Huseni M, Totpal K, Du C, Dalpozzo K, Zhu J, Rishipathak D, McNamara E, Jonshtone B, Hegde PS, Rhee I. (2014) Anti-tumor efficacy and biomarker evaluation of agonistic anti-OX40 antibodies in preclinical models. Journal for Immunotherapy of Cancer, 2 (Suppl 3): 105.

6. Nakagawa H, Iizuka H, Nemoto O, Shimabe M, Furukawa Y, Kikuta N, Ootaki K. (2020) Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J Dermatol Sci, 99 (2): 82-89. [PMID:32651105]

7. Papp KA, Gooderham MJ, Girard G, Raman M, Strout V. (2017) Phase I randomized study of KHK4083, an anti-OX40 monoclonal antibody, in patients with mild to moderate plaque psoriasis. J Eur Acad Dermatol Venereol, 31 (8): 1324-1332. [PMID:28556418]

8. Song Y, Margolles-Clark E, Bayer A, Buchwald P. (2014) Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction. Br J Pharmacol, 171 (21): 4955-69. [PMID:24930776]

9. Webb GJ, Hirschfield GM, Lane PJ. (2016) OX40, OX40L and Autoimmunity: a Comprehensive Review. Clin Rev Allergy Immunol, 50 (3): 312-32. [PMID:26215166]

Contributors

Show »

How to cite this page