ReviewFrontiers in immunology2023
Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.
Review in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular Architecture and Clinical Landscape of Immune Checkpoint Receptors and Ligands.Antibodies (Basel, Switzerland) · 2026Review
- Both soluble and cell surface CD137 expressed by Foxp3+ CD4 T cells restrain autoimmune diabetes.The Journal of experimental medicine · 2026Article
- MIF tautomerase inhibitor 4-IPP alleviates HFD-induced obesity by restoring CD137-mediated browning of white adipocytes in mice.Acta pharmacologica Sinica · 2026Article
- Elevated Serum Soluble CD137 in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis Highlights a Shared Immunoregulatory Signature.Biomedicines · 2026Article
- Unraveling the inflammatory bridge: genomic evidence identifies TNFRSF9 as a potential biomarker linking Sjögren's syndrome to total risk non-Hodgkin lymphoma.Clinical rheumatology · 2026Article
- Pediatric bronchiolitis disease severity is associated with immune checkpoint dysregulation.Pediatric research · 2026Article
- Extended treatment of abrocitinib: evaluation of efficacy and safety in chronic actinic dermatitis.Frontiers in medicine · 2026Article
- Identification and validation of prognostic genes associated with clear cell renal cell carcinoma: based on public whole transcriptome sequencing datasets.Frontiers in oncology · 2026Article
- Induction of cell death in malignant cells and regulatory T cells in the tumor microenvironment by targeting CD137.Oncoimmunology · 2025Article
- Myelodysplastic Neoplasms (MDS): Pathogenesis and Therapeutic Prospects.Biomolecules · 2025Review
- Enhanced durability of a Zika virus self-amplifying RNA vaccine through combinatorial OX40 and 4-1BB agonism.JCI insight · 2025Article
- A Phase I Clinical Trial Adding OX40 Agonism to In Situ Therapeutic Cancer Vaccination in Patients with Low-Grade B-cell Lymphoma Highlights Challenges in Translation from Mouse to Human Studies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- Emerging druggable targets for immune checkpoint modulation in cancer immunotherapy: the iceberg lies beneath the surface.Apoptosis : an international journal on programmed cell death · 2024Review
- Tumor necrosis factor superfamily signaling: life and death in cancer.Cancer metastasis reviews · 2024Review
- Novel engineered IL-2 Nemvaleukin alfa combined with PD1 checkpoint blockade enhances the systemic anti-tumor responses of radiation therapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy.Science advances · 2024Article
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
- ATOR-1017 (evunzekibart), an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1.Cancer immunology, immunotherapy : CII · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Costimulatory receptors on immune cells represent attractive targets for immunotherapy given that these molecules can increase the frequency of individual protective immune cell populations and their longevity, as well as enhance various effector functions. 4-1BB, a member of the TNF receptor superfamily, also known as CD137 and TNFRSF9, is one such molecule that is inducible on several cell types, including T cells and NK cells. Preclinical studies in animal models have validated the notion that stimulating 4-1BB with agonist reagents or its natural ligand could be useful to augment conventional T cell and NK cell immunity to protect against tumor growth and against viral infection. Additionally, stimulating 4-1BB can enhance regulatory T cell function and might be useful in the right context for suppressing autoimmunity. Two human agonist antibodies to 4-1BB have been produced and tested in clinical trials for cancer, with variable results, leading to the production of a wealth of second-generation antibody constructs, including bi- and multi-specifics, with the hope of optimizing activity and selectivity. Here, we review the progress to date in agonism of 4-1BB, discuss the complications in targeting the immune system appropriately to elicit the desired activity, together with challenges in engineering agonists, and highlight the untapped potential of manipulating this molecule in infectious disease and autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.