ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 16 citations in OpenAlex.
- Integrated bioinformatics analysis and clinical validation identifies TNFSF14 and CD40 as novel biomarkers for chronic kidney disease progression and tubulointerstitial injury.International urology and nephrology · 2026Article
- Immunogenicity and protective efficacy on non-adjuvanted CD40-targeting SARS-CoV-2 vaccines in non-human primates.EBioMedicine · 2026Article
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Article
- Ponatinib Averts αCD40 Antibody Mediated Toxicity by Lowering MAPK38 Expression and Shows Proimmunogenic Effects in a Murine Tumor Model.ACS pharmacology & translational science · 2025Article
- Synergy and antagonism in the integration of BCR and CD40 signals that control B-cell population expansion.Molecular systems biology · 2025Article
- Microbead-based synthetic niches for in vitro expansion and differentiation of human naïve B-cells.Bioengineering & translational medicine · 2025Article
- Therapeutic potential of TNFR2 agonists: a mechanistic perspective.Frontiers in immunology · 2023Review
- Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine.EBioMedicine · 2022Article
- γδ T cell costimulatory ligands in antitumor immunity.Exploration of immunology · 2022Article
- Refining the DC-targeting vaccination for preventing emerging infectious diseases.Frontiers in immunology · 2022Review
- A Framework to Identify Antigen-Expanded T Cell Receptor Clusters Within Complex Repertoires.Frontiers in immunology · 2021Article
- Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines.Frontiers in immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD40 is a potent activating receptor within the TNFR family expressed on APCs of the immune system, and it regulates many aspects of B and T cell immunity via interaction with CD40 ligand (CD40L; CD154) expressed on the surface of activated T cells. Soluble CD40L and agonistic mAbs directed to CD40 are being explored as adjuvants in therapeutic or vaccination settings. Some anti-CD40 Abs can synergize with soluble monomeric CD40L. We show that direct fusion of CD40L to certain agonistic anti-CD40 Abs confers superagonist properties, reducing the dose required for efficacy, notably greatly increasing total cytokine secretion by human dendritic cells. The tetravalent configuration of anti-CD40-CD40L Abs promotes CD40 cell surface clustering and internalization and is the likely mechanism of increased receptor activation. CD40L fused to either the L or H chain C termini, with or without flexible linkers, were all superagonists with greater potency than CD40L trimer. The increased anti-CD40-CD40L Ab potency was independent of higher order aggregation. Moreover, the anti-CD40-CD40L Ab showed higher potency in vivo in human CD40 transgenic mice compared with the parental anti-CD40 Ab. To broaden the concept of fusing agonistic Ab to natural ligand, we fused OX40L to an agonistic OX40 Ab, and this resulted in dramatically increased efficacy for proliferation and cytokine production of activated human CD4
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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.