ArticleJournal of immunology (Baltimore, Md. : 1950)2007
Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice.
Article in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 170 citations in OpenAlex.
- Importance of the delivery route for the tolerability and efficacy of immunomodulatory agents for lung cancer.Scientific reports · 2026Article
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- Elucidating the Mechanisms of SA-4-1BBL-Mediated Cancer Immunoprevention Through Advanced Informatics Approaches.Biomolecules · 2026Article
- Phase 1 Study of INBRX-105, a TNFRSF9 (4-1BB) and PD-L1 Bispecific Antibody, in Patients with Select Solid Tumors.Cancer research communications · 2026Article
- Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy.Journal of hematology & oncology · 2024Review
- Final results of urelumab, an anti-CD137 agonist monoclonal antibody, in combination with cetuximab or nivolumab in patients with advanced solid tumors.Journal for immunotherapy of 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
- Sensitize Tumor Immunotherapy: Immunogenic Cell Death Inducing Nanosystems.International journal of nanomedicine · 2024Review
- Engineered soluble, trimerized 4-1BBL variants as potent immunomodulatory agents.Cancer immunology, immunotherapy : CII · 2023Article
- Agonism of 4-1BB for immune therapy: a perspective on possibilities and complications.Frontiers in immunology · 2023Review
- NK Cell-Targeted Immunotherapies in Bladder Cancer: Beyond Checkpoint Inhibitors.Bladder cancer (Amsterdam, Netherlands) · 2023Review
- Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors.Cancer discovery · 2022Article
- In vivo imaging with two-photon microscopy to assess the tumor-selective binding of an anti-CD137 switch antibody.Scientific reports · 2022Article
- CD137 agonist potentiates the abscopal efficacy of nanoparticle-based photothermal therapy for melanoma.Nano research · 2022Article
- Antibody-Targeted TNFRSF Activation for Cancer Immunotherapy: The Role of FcγRIIB Cross-Linking.Frontiers in pharmacology · 2022Review
- Fc-based Duokines: dual-acting costimulatory molecules comprising TNFSF ligands in the single-chain format fused to a heterodimerizing Fc (scDk-Fc).Oncoimmunology · 2022Article
- The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.Cell reports. Medicine · 2021Article
- Immunoprofiling of 4-1BB Expression Predicts Outcome in Chronic Lymphocytic Leukemia (CLL).Diagnostics (Basel, Switzerland) · 2021Article
- Switchable immune modulator for tumor-specific activation of anticancer immunity.Science advances · 2021Article
- Anti-tumor effects of RTX-240: an engineered red blood cell expressing 4-1BB ligand and interleukin-15.Cancer immunology, immunotherapy : CII · 2021Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
CD137-mediated signals costimulate T cells and protect them from activation-induced apoptosis; they induce curative antitumor immunity and enhance antiviral immune responses in mice. In contrast, anti-CD137 agonistic mAbs can suppress T-dependent humoral immunity and reverse the course of established autoimmune disease. These results have provided a rationale for assessing the therapeutic potential of CD137 ligands in human clinical trials. In this study, we report that a single 200-mug injection of anti-CD137 given to otherwise naive BALB/c or C57BL/6 mice led to the development of a series of immunological anomalies. These included splenomegaly, lymphadenopathy, hepatomegaly, multifocal hepatitis, anemia, altered trafficking of B cells and CD8 T cells, loss of NK cells, and a 10-fold increase in bone marrow (BM) cells bearing the phenotype of hemopoietic stem cells. These events were dependent on CD8 T cells, TNF-alpha, IFN-gamma, and type I IFNs. BM cells up-regulated Fas, and there was a significant increase in the number of CD8+ T cells that correlated with a loss of CD19+ and Ab-secreting cells in the BM. TCR Valphabeta usage was random and polyclonal among liver-infiltrating CD8 T cells, and multifocal CD8+ T cell infiltrates were resolved upon termination of anti-CD137 treatment. Anti-CD137-treated mice developed lymphopenia, thrombocytopenia, and anemia, and had lowered levels of hemoglobin and increased numbers of reticulocytes.
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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.