ArticleVaccine2009
A novel form of 4-1BBL has better immunomodulatory activity than an agonistic anti-4-1BB Ab without Ab-associated severe toxicity.
Article in Vaccine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Elucidating the Mechanisms of SA-4-1BBL-Mediated Cancer Immunoprevention Through Advanced Informatics Approaches.Biomolecules · 2026Article
- Oncolytic Adenovirus Armed with a Novel Agonist of the CD137 Immune Checkpoint Stimulator Suppresses Tumor Growth.Vaccines · 2024Article
- A novel agonist of 4-1BB costimulatory receptor shows therapeutic efficacy against a tobacco carcinogen-induced lung cancer.Cancer immunology, immunotherapy : CII · 2023Article
- Development of an antibody-ligand fusion protein scFvCD16AMicrobial cell factories · 2023Article
- 4-1BBL as a Mediator of Cross-Talk between Innate, Adaptive, and Regulatory Immunity against Cancer.International journal of molecular sciences · 2021Review
- Meeting Report: Translational Advances in Cancer Prevention Agent Development Meeting.Journal of cancer prevention · 2021Article
- Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors.Frontiers in cell and developmental biology · 2021Review
- Article
- A Novel Form of 4-1BBL Prevents Cancer Development via Nonspecific Activation of CD4Cancer research · 2019Article
- Article
- Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.Nature communications · 2018Article
- Current perspectives of SA-4-1BBL in immune modulation during cancer.Experimental and therapeutic medicine · 2018Article
- Stimulation of natural killer cells with rhCD137 ligand enhances tumor-targeting antibody efficacy in gastric cancer.PloS one · 2018Article
- 4-1BB Signaling in Conventional T Cells Drives IL-2 Production That Overcomes CD4+CD25+FoxP3+ T Regulatory Cell Suppression.PloS one · 2016Article
- 4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity.Frontiers in oncology · 2015Review
- SA-4-1BBL and monophosphoryl lipid A constitute an efficacious combination adjuvant for cancer vaccines.Cancer research · 2014Article
- Galectin-9 controls the therapeutic activity of 4-1BB-targeting antibodies.The Journal of experimental medicine · 2014Article
- SA-4-1BBL as a novel adjuvant for the development of therapeutic cancer vaccines.Expert review of vaccines · 2014Review
- 4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Agonistic Abs to select costimulatory members of CD28 and TNFR family have shown efficacy in various preclinical cancer immunotherapeutic settings. However, the use of agonistic Abs is often associated with severe toxicity due to non-specific activation of lymphocytes. We hypothesized that natural costimulatory ligands may serve as more potent and safer alternative to agonistic Abs for immunotherapy. In this communication, we focused on 4-1BBL as the molecule of choice because of the pleiotropic effects of 4-1BB signaling in the immune system and the demonstrated therapeutic efficacy of 4-1BB agonistic Abs in preclinical cancer and infection models. We report that a novel form of soluble ligand, SA-4-1BBL, delivered more potent and qualitatively different signals to T cells than an agonistic Ab. Importantly, while treatment of naïve mice with the agonistic Ab resulted in severe toxicity, as assessed by enlarged spleen and peripheral LNs, non-specific T cell proliferation, hepatitis, and systemic inflammatory cytokine production, treatment with SA-4-1BBL lacked these immune anomalies. Agonistic Ab treatment produced full toxicity in FcgammaR(-/-) or complement C1q(-/-) or C3(-/-) knockout mice, suggesting lack of involvement of stimulatory FcgammaRs or complement system in the observed toxicity. Naïve and memory T cells served as direct targets of anti-4-1BB Ab-mediated toxicity. Potent immunostimulatory activity combined with lack of toxicity rationalizes further development of soluble SA-4-1BBL as an immunomodulatory component of therapeutic vaccines against cancer and chronic infections.
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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.