ArticleCancer immunology research2014
Role of crosslinking for agonistic CD40 monoclonal antibodies as immune therapy of cancer.
Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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.
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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
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Agonistic anti-CD40 antibodies in patients with solid tumors: a systematic review and evidence map of clinical safety, with exploratory proportional synthesis.Frontiers in immunology · 2026Pooled it
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Article
- Clinical applications and challenges of CD40/CD40L signaling regulation in autoimmune diseases.Frontiers in immunology · 2026Review
- The spontaneous neoantigen-specific CD4Journal for immunotherapy of cancer · 2025Article
- Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024Review
- Fcγ receptors and immunomodulatory antibodies in cancer.Nature reviews. Cancer · 2024Review
- Development of a Cytotoxic Antibody-Drug Conjugate Targeting Membrane Immunoglobulin E-Positive Cells.International journal of molecular sciences · 2023Article
- Selective Internal Radiotherapy Alters the Profiles of Systemic Extracellular Vesicles in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Article
- Effect of posttranslational modifications and subclass on IgG activity: from immunity to immunotherapy.Nature immunology · 2023Review
- Cell targeting and immunostimulatory properties of a novel Fcγ-receptor-independent agonistic anti-CD40 antibody in rhesus macaques.Cellular and molecular life sciences : CMLS · 2023Article
- Delivering co-stimulatory tumor necrosis factor receptor agonism for cancer immunotherapy: past, current and future perspectives.Frontiers in immunology · 2023Review
- Mechanisms of action of monoclonal antibodies in oncology integrated in IMGT/mAb-DB.Frontiers in immunology · 2023Article
- Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation.Nature reviews. Cancer · 2022Review
- FcγRs and Their Relevance for the Activity of Anti-CD40 Antibodies.International journal of molecular sciences · 2022Review
- Developing a translational murine-to-canine pathway for an IL-2/agonist anti-CD40 antibody cancer immunotherapy.Veterinary and comparative oncology · 2022Article
- Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets.Journal of hematology & oncology · 2022Review
- CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies.Cellular & molecular immunology · 2022Review
- Antibody-Targeted TNFRSF Activation for Cancer Immunotherapy: The Role of FcγRIIB Cross-Linking.Frontiers in pharmacology · 2022Review
- Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Agonists of the TNF superfamily of receptors hold promise as novel therapy for cancer. Recent data on agonistic anti-murine TNF receptors (TNFR) such as CD40 suggest that the specific engagement of Fc-receptor (FcR) is required for optimal antitumor effects, prompting calls to engineer anti-human CD40 and other TNFR mAb accordingly. CP-870,893 is a fully human anti-CD40 mAb, selected in part because it is an IgG2 which is presumed to have poor reactivity with FcR; however, CP-870,893 has been evaluated in multiple clinical trials with beneficial activity in patients with melanoma, pancreatic and other cancers. Here, we confirmed that the activity of anti-murine CD40 mAb was dependent on FcγRIIB engagement, was decreased significantly in FcγRIIB (-/-) mice, and upon Fc-crosslinking anti-mouse CD40 mAb enhanced the activation of antigen presenting cells. In contrast, the CP-870,893-mediated activation of human B cells was not enhanced with anti-IgG-crosslinking nor abrogated when used as an F(ab)'2 reagent. Crosslinking of CP-870,893 using the CD32-expressing K562 cells yielded an Fc-dependent modest increase in the expression of some activation markers relative to that of the soluble CP-870,893 mAb. Classic Fc-dependent functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) were minimal for CP-870,893 as compared to the IgG1 anti-CD20 mAb rituximab, which mediated both ADCC and CMC in parallel assays. Anti-mouse CD40 mAb competed for the CD40 ligand binding site, but CP-870,893 did not. Thus, Fc-crosslinking is not an essential requirement for agonistic anti-human CD40 mAb, whose potency is more dependent on the CD40 epitope recognized and the strength of the signal achieved.
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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.