ArticleNature communications2018
Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
95 citing papers in PubMed, 143 citations in OpenAlex.
- FTL008.16, a 5T4-Conditional 4-1BB bispecific antibody, potently enhances antitumor immunity via tumor-directed t-cell activation.Oncoimmunology · 2026Article
- Review
- Bridging BET bromodomain and immune checkpoint inhibitors through generative bioorganic frameworks for next-generation cancer immunotherapy.RSC medicinal chemistry · 2026Review
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Agonistic bispecific antibodies: an emerging frontier in antibody therapeutics.Journal of translational medicine · 2026Review
- Expression of the immune checkpoint CD137/CD137L in oral squamous cell carcinoma (OSCC) and association with histopathological parameters.Virchows Archiv : an international journal of pathology · 2026Article
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Bispecific targeting of 4-1BB and CCR8 boosts antitumor immunity via Ti-Treg depletion and CD8iScience · 2025Article
- An iterative strategy to design 4-1BB agonist nanobodies de novo with generative AI models.Scientific reports · 2025Article
- Fragment-Based Immune Cell Engager Antibodies in Treatment of Cancer, Infectious and Autoimmune Diseases: Lessons and Insights from Clinical and Translational Studies.Antibodies (Basel, Switzerland) · 2025Review
- Inducing Cancer Cell Killing Using DNA Nanostructure-Mediated Superclustering of Death Receptors.Nano letters · 2025Article
- MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137.International journal of molecular sciences · 2025Article
- CD137-expressing regulatory T cells in cancer and autoimmune diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families.Frontiers in immunology · 2025Review
- Polymeric Multivalent Fc Binding Peptides-Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA-4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Small molecules from antibody pharmacophores (SMAbPs) as a hit identification workflow for immune checkpoints.Science advances · 2024Article
- Enhanced IL-15-mediated NK cell activation and proliferation by an ADAM17 function-blocking antibody involves CD16A, CD137, and accessory cells.Journal for immunotherapy of cancer · 2024Article
- Emerging Targets and Therapeutics in Immuno-Oncology: Insights from Landscape Analysis.Journal of medicinal chemistry · 2024Review
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate utomilumab is a milder agonist than urelumab. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.
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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.