ArticleJournal for immunotherapy of cancer2020
CD40 agonist-induced IL-12p40 potentiates hepatotoxicity.
Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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
20 citing papers in PubMed, 22 citations in OpenAlex.
- A phase 2 trial of CXCR4 antagonism and PD1 inhibition in metastatic pancreatic adenocarcinoma reveals recruitment of T cells but also immunosuppressive macrophages.Oncoimmunology · 2025Trial
- Docetaxel-Induced Immune Activation Shows Antitumor Synergy With the Tumor-Targeted CD40 Agonist KK2269.Cancer science · 2026Article
- Article
- Article
- Next-Generation Immune Checkpoints and Tumor Microenvironment Modulation in Cancer Immunotherapy.Journal of immunology research · 2026Review
- Targeting the CD40 costimulatory receptor to improve virotherapy efficacy in diffuse midline gliomas.Cell reports. Medicine · 2025Article
- Facts and Hopes of CD40 Agonists in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Emerging therapeutics targeting tumor-associated macrophages for the treatment of solid organ cancers.Expert opinion on emerging drugs · 2025Review
- Research advances in immune agonists and their nanoparticles for enhancing the immunotherapeutic efficacy of PD-1 inhibitors in malignancies.Frontiers in oncology · 2025Review
- Genetically engineered IgG1 and nanobody oligomers acquire strong intrinsic CD40 agonism.Bioengineered · 2024Article
- Improved safety of chimeric antigen receptor T cells indirectly targeting antigens via switchable adapters.Nature communications · 2024Article
- Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024Review
- Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity.Journal for immunotherapy of cancer · 2023Article
- FcγRs and Their Relevance for the Activity of Anti-CD40 Antibodies.International journal of molecular sciences · 2022Review
- Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Review
- Next Generation CD40 Agonistic Antibodies for Cancer Immunotherapy.Frontiers in immunology · 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
- Review
- Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy.Science 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
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD40 is a compelling target for cancer immunotherapy, however, attempts to successfully target this pathway have consistently been hampered by dose-limiting toxicity issues in the clinic that prevents the administration of efficacious doses.
methodsHere, using cytokine and cytokine receptor depletion strategies in conjunction with a potent CD40 agonist, we investigated mechanisms underlying the two primary sources of CD40 agonist-associated toxicity, hepatotoxicity and cytokine release syndrome (CRS).
resultsWe demonstrate that CD40 agonist -induced hepatotoxicity and CRS are mechanistically independent. Historical data have supported a role for interleukin-6 (IL-6) in CRS-associated wasting, however, our findings instead show that an inflammatory cytokine network involving TNF, IL-12p40, and IFNγ underlie this process. Deficiency of TNF or IFNγ did not influence CD40-induced hepatitis however loss of IL-12p40 significantly decreased circulating concentrations of liver enzymes and reduced the frequency of activated CD14
conclusionsAs clinical research programs aim to circumnavigate toxicity concerns while maintaining antitumor efficacy it will be essential to understand which features of CD40 biology mediate antitumor function to develop both safe and efficacious agonists.
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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.