ReviewFrontiers in immunology2023
Targeting CD137 (4-1BB) towards improved safety and efficacy for cancer immunotherapy.
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 18 papers.
What it found
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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
18 citing papers in PubMed, 18 citations in OpenAlex.
- Agonistic bispecific antibodies: an emerging frontier in antibody therapeutics.Journal of translational medicine · 2026Review
- Bispecific antibody AP402 targets p95HER2 and induces costimulation through CD137 to improve efficacy for HER2-positive tumors.Molecular medicine (Cambridge, Mass.) · 2026Article
- Improved expansion of peripheral blood and iPSC-derived natural killer cells for clinical applications.Cell reports methods · 2026Article
- A Comprehensive Literature Review and Case Report of Severe Lymphoproliferative Disease Secondary toJournal of clinical medicine · 2026Article
- Review
- Decoding the crosstalk between ubiquitination and other post-translational modifications in cancer immunity: from mechanisms to clinical prospects.NPJ precision oncology · 2026Review
- Diabetes exacerbates destructive inflammation by activating the CD137L-CD137 axis in dendritic and IL-17+ T cells.The Journal of clinical investigation · 2026Article
- The tumor microenvironment as a key regulator of radiotherapy response.Frontiers in immunology · 2026Review
- Immune cell engagers in lung cancer.Frontiers in immunology · 2026Review
- Multidimensional applications of prussian blue-based nanoparticles in cancer immunotherapy.Journal of nanobiotechnology · 2025Review
- 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
- CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?Frontiers in immunology · 2025Review
- 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
- Modeling T cell temporal response to cancer immunotherapy rationalizes development of combinatorial treatment protocols.Nature cancer · 2024Article
- Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin's lymphoma.Cell reports. Medicine · 2024Article
- 4-1BB immunotherapy: advances and hurdles.Experimental & molecular medicine · 2024Review
- Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cells play a critical role in antitumor immunity, where T cell activation is regulated by both inhibitory and costimulatory receptor signaling that fine-tune T cell activity during different stages of T cell immune responses. Currently, cancer immunotherapy by targeting inhibitory receptors such as CTLA-4 and PD-1/L1, and their combination by antagonist antibodies, has been well established. However, developing agonist antibodies that target costimulatory receptors such as CD28 and CD137/4-1BB has faced considerable challenges, including highly publicized adverse events. Intracellular costimulatory domains of CD28 and/or CD137/4-1BB are essential for the clinical benefits of FDA-approved chimeric antigen receptor T cell (CAR-T) therapies. The major challenge is how to decouple efficacy from toxicity by systemic immune activation. This review focuses on anti-CD137 agonist monoclonal antibodies with different IgG isotypes in clinical development. It discusses CD137 biology in the context of anti-CD137 agonist drug discovery, including the binding epitope selected for anti-CD137 agonist antibody in competition or not with CD137 ligand (CD137L), the IgG isotype of antibodies selected with an impact on crosslinking by Fc gamma receptors, and the conditional activation of anti-CD137 antibodies for safe and potent engagement with CD137 in the tumor microenvironment (TME). We discuss and compare the potential mechanisms/effects of different CD137 targeting strategies and agents under development and how rational combinations could enhance antitumor activities without amplifying the toxicity of these agonist antibodies.
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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.