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OX40: From Setbacks in Cancer Immunotherapy to a New Hope in Autoimmune Diseases

Release date: 2025-04-27 View count: 84
OX40 (CD134) is a member of the tumor necrosis factor receptor (TNFR) superfamily and serves as a crucial T-cell costimulatory molecule. It is predominantly expressed on activated CD4+ and CD8+ T cells. Its ligand, OX40L (CD252), is mainly expressed on antigen-presenting cells (APCs) such as B cells, dendritic cells, and macrophages. Upon binding to OX40L, OX40 triggers downstream signaling pathways that promote T cell survival, proliferation, and the secretion of cytokines like IL-2, IL-4, IL-5, and IFN-γ, making it a key target in OX40 immunotherapy research.
OX40 and OX40L interaction on T cells and APCs
Figure 1: OX40 expression is induced on activated T cells, while OX40L expression is induced on APCs. Their interaction stimulates the clonal expansion of effector CD4+ and CD8+ T cells, upregulates proinflammatory cytokines, and enhances T cell survival.
Once a rising star in the field of immunotherapy, OX40 rapidly became a hot target for drug development. Its ability to robustly regulate CD4+ and CD8+ T cell survival and expansion — demonstrated across multiple animal models of infection, cancer, and autoimmune diseases — fueled high expectations. Major pharmaceutical companies eagerly invested in developing OX40 agonists, hoping to revolutionize cancer immunotherapy.
However, clinical outcomes fell short of expectations. Poor efficacy combined with frequent adverse effects meant that no OX40 agonist has successfully advanced beyond Phase II clinical trials. In January 2019, Pfizer announced the termination of its OX40 agonist PF-04518600 after a disappointing Phase I trial, where the objective response rate was only 5.8%, with most patients showing no response. Subsequently, other companies like Bristol-Myers Squibb, GSK, and AstraZeneca also halted their OX40 agonist programs due to similar failures.
Pfizer discontinuing OX40 agonist program
Figure 2: Pfizer announces the discontinuation of its OX40 agonist program.
Despite setbacks in oncology, OX40 inhibitors have brought renewed hope for the target — this time in the realm of autoimmune diseases. On June 27, 2023, Sanofi announced that its OX40 inhibitor, Amlitelimab achieved success in a Phase 2b trial (STREAM-AD) for moderate-to-severe atopic dermatitis, meeting both primary and key secondary endpoints at weeks 16 and 24. Amlitelimab thus joins Rocatinlimab as the second OX40 inhibitor to successfully complete a Phase 2 trial.
Rocatinlimab works by selectively reducing activated OX40+ T cells, inhibiting T cell proliferation, and lowering inflammatory cytokine production. Amlitelimab targets OX40L to block T cell activation and restore immune homeostasis. Notably, Kymab, the original developer of Amlitelimab, was acquired by Sanofi early in the clinical development phase, underscoring the high potential seen in the molecule. The success of OX40 inhibitors in treating autoimmune diseases has reignited industry interest, drawing more companies into this promising field.
Alongside clinical advances, the emergence of functional antibodies has provided researchers with powerful new tools to study OX40 signaling. Compared to transgenic mouse models, functional antibodies offer several significant advantages: reduced complexity, lower cost, shorter timelines, and direct mechanistic control.
OX40 functional antibodies are classified into two types:
  • Agonistic antibodies: Bind to OX40 and activate its signaling pathways.
  • Blocking antibodies: Bind to OX40L and inhibit OX40 activation.
These tools have been widely used to investigate T cell activation, proliferation, and immune memory, with key features such as:
  • High specificity: Precisely targeting OX40 without affecting other pathways.
  • Direct modulation: Allowing controlled activation or inhibition of OX40 signaling.
  • Fine-tuned control: Enabling researchers to adjust timing and dosage for optimal therapeutic strategy development.
  • Broad applicability: Suitable for in vitro studies, animal models, and clinical research, and amenable to combination therapy exploration.
As a core brand under ProteoGenix (France), abinScience focuses on developing and manufacturing high-quality reagents for in vivo research. Its extensive antibody library — covering over 400 validated antibodies — includes key clones such as:
  • Immune checkpoint antibodies: PD-1/PD-L1 (10F9G2, RMP1-14, D12)
  • Functional blocking antibodies: IFN-γ (XMG1.2), CD16/CD32 (2.4G2)
  • Cytokine antibodies: IL-2 (ES6-1A12), CD40 (FGK45)
  • T-cell activation antibodies: CD3 (UCHT-1), CD25 (PC61)
Each product undergoes strict validation to ensure purity, specificity, and functionality. Available in milligram to gram scales, abinScience reagents are ideal for disease mechanism studies, immunoassays, and drug development — all in stock for rapid delivery.
Below is a selection of OX40-related products offered by abinScience, including functional antibodies, in vivo-grade antibodies, research-grade monoclonal antibodies, recombinant proteins, and positive controls. For more information, contact our specialists!
Antibody:
Catalog No. Product Name
MW342107 Anti-Mouse CD134/TNFRSF4/OX40 Antibody (OX-86)
MW342014 Anti-Mouse CD134/TNFRSF4/OX40 Polyclonal Antibody
HW342307 Anti-Human CD134/TNFRSF4/OX40 Antibody (3C8)
HW342117 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0762), FITC
HW342217 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS2105), FITC
HW342317 Anti-Human CD134/TNFRSF4/OX40 Antibody (3C8), FITC
MW342117 Anti-Mouse CD134/TNFRSF4/OX40 Antibody (OX-86), FITC
HW342013 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0255)
HW342127 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0762), PE
HW342227 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS2105), PE
HW342327 Anti-Human CD134/TNFRSF4/OX40 Antibody (3C8), PE
MW342127 Anti-Mouse CD134/TNFRSF4/OX40 Antibody (OX-86), PE
HW342147 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0762), PerCP
HW342247 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS2105), PerCP
HW342347 Anti-Human CD134/TNFRSF4/OX40 Antibody (3C8), PerCP
MW342147 Anti-Mouse CD134/TNFRSF4/OX40 Antibody (OX-86), PerCP
HW342137 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0762), APC
HW342237 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS2105), APC
HW342337 Anti-Human CD134/TNFRSF4/OX40 Antibody (3C8), APC
MW342137 Anti-Mouse CD134/TNFRSF4/OX40 Antibody (OX-86), APC
HW342107 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS0762)
HW342207 Anti-Human CD134/TNFRSF4/OX40 Antibody (ABS2105)
MB651040 InVivoMAb Anti-Mouse CTLA4 & OX40 Bispecific Antibody (ABV0058)
MW754030 InVivoMAb Anti-Mouse TRP-1 & OX40 Bispecific Antibody (ABV0259)
MW342010 InVivoMAb Anti-Mouse PD-L1 & OX40 Bispecific Antibody (ABV0223)
HW342086 Research Grade Anti-Human CD134/TNFRSF4/OX40 (INCAGN1949)
HW342096 Research Grade Anti-Human CD134/TNFRSF4/OX40 (BAT6026)
HW342106 Research Grade Anti-Human CD134/TNFRSF4/OX40 (BMS 986178)
HW342126 Research Grade Anti-Human CD134/TNFRSF4/OX40 (INBRX-106)
HW342136 Research Grade Anti-Human CD134/TNFRSF4/OX40 (YH-002)
HW342146 Research Grade Anti-Human CD134/TNFRSF4/OX40 (GSK 3174998)
HW342156 Research Grade Anti-Human CD134/TNFRSF4/OX40 (HFB301001)
HW342166 Research Grade Anti-Human CD134/TNFRSF4/OX40 (MSB013)
HW342176 Research Grade Anti-Human CD134/TNFRSF4/OX40 (MEDI 6469)
HW342186 Research Grade Anti-Human CD134/TNFRSF4/OX40 (ZL-1101)
HW342196 Research Grade Gimistotug
HW342076 Research Grade Rocatinlimab
HW342016 Research Grade Ivuxolimab
HW342026 Research Grade Pogalizumab
HW342036 Research Grade Tavolimab
HW342046 Research Grade Cudarolimab
HW342056 Research Grade Revdofilimab
HW342066 Research Grade Telazorlimab
Abs0264 Pogalizumab Biosimilar, Anti-CD134/TNFRSF4/OX40
Abs0266 Cudarolimab Biosimilar, Anti-CD134/TNFRSF4/OX40
Abs0267 Telazorlimab Biosimilar, Anti-CD134/TNFRSF4/OX40
Protein:
Catalog No. Product Name
ZW342012 Recombinant Red fox CD134/TNFRSF4/OX40 Protein, C-His
CW342012 Recombinant Dog CD134/TNFRSF4/OX40 Protein, C-Fc
MW342012 Recombinant Mouse CD134/TNFRSF4/OX40 Protein, N-His
HW342011 Recombinant Human CD134/TNFRSF4/OX40 Protein, C-His
MW342011 Recombinant Mouse CD134/TNFRSF4/OX40 Protein, C-Fc
HB937021 Recombinant Human CD252/TNFSF4/OX40L Protein, C-His
HB937012 Recombinant Human CD252/TNFSF4 Protein, N-His
HB937011 Recombinant Human CD252/TNFSF4 Protein, N-Fc
References on OX40 Immunotherapy and T-Cell Research:
  1. Fu, Y., Lin, Q., Zhang, Z., and Zhang, L. (2020). Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity. Acta Pharm Sin B, 10, 414-433. doi:10.1016/j.apsb.2019.08.010
  2. Gress, A.R., Ronayne, C.E., Thiede, J.M., Meyerholz, D.K., Okurut, S., Stumpf, J., Mathes, T.V., Ssebambulidde, K., Meya, D.B., Cresswell, F.V., et al. (2023). Recently activated CD4 T cells in tuberculosis express OX40 as a target for host-directed immunotherapy. Nat Commun, 14, 8423. doi:10.1038/s41467-023-44152-8
  3. Gracias, D.T., Sethi, G.S., Mehta, A.K., Miki, H., Gupta, R.K., Yagita, H., and Croft, M. (2021). Combination blockade of OX40L and CD30L inhibits allergen-driven memory T(H)2 cell reactivity and lung inflammation. J Allergy Clin Immunol, 147, 2316-2329. doi:10.1016/j.jaci.2020.10.037

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