ArticleBMC molecular and cell biology2019
CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches.
Article in BMC molecular and cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Efficacy and Safety of Ravagalimab in Patients with Moderate-to-Severe Ulcerative Colitis: Data from a Phase 2a Trial.Advances in therapy · 2026Trial
- Clinical applications and challenges of CD40/CD40L signaling regulation in autoimmune diseases.Frontiers in immunology · 2026Review
- EMoMiS: A pipeline for epitope-based molecular mimicry search in protein structures with potential applications to SARS-CoV-2.Computational and structural biotechnology journal · 2026Article
- Ligand non-competitive GITR antibody prevents formation of the obligatory signal-triggering GITRL: GITR stoichiometry.Scientific reports · 2025Article
- The CD40/CD40L Pathway Regulates the Aggressiveness of Ovarian Cancer Cells via the Activation of Regulatory B Cells.Biochemical genetics · 2025Article
- Structure of the Fab fragment of a humanized 5E5 antibody to a cancer-specific Tn-MUC1 epitope.Acta crystallographica. Section D, Structural biology · 2025Article
- Potential biomarkers of recurrent FSGS: a review.BMC nephrology · 2024Review
- Intrafamily heterooligomerization as an emerging mechanism of methyltransferase regulation.Epigenetics & chromatin · 2024Review
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- CD40/CD40L expression and its prognostic value in cervical cancer.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- The benefits of clustering in TNF receptor superfamily signaling.Frontiers in immunology · 2023Review
- FcγRs and Their Relevance for the Activity of Anti-CD40 Antibodies.International journal of molecular sciences · 2022Review
- Landscape of human antibody recognition of the SARS-CoV-2 receptor binding domain.Cell reports · 2021Article
- Anti-CD40 antibody KPL-404 inhibits T cell-mediated activation of B cells from healthy donors and autoimmune patients.Arthritis research & therapy · 2021Article
- Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.Signal transduction and targeted therapy · 2020Review
- Review
- HSP70 Multi-Functionality in Cancer.Cells · 2020Review
- Transcriptional splice variants of CD40 and its prognostic value in breast cancer.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD40 is a 48 kDa type I transmembrane protein that is constitutively expressed on hematopoietic cells such as dendritic cells, macrophages, and B cells. Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases. CD40 antagonists are currently being explored for the treatment of autoimmune diseases and several anti-CD40 agonist mAbs have entered clinical development for oncological indications.
resultsTo better understand the mode of action of anti-CD40 mAbs, we have determined the x-ray crystal structures of the ABBV-323 (anti-CD40 antagonist, ravagalimab) Fab alone, ABBV-323 Fab complexed to human CD40 and FAB516 (anti-CD40 agonist) complexed to human CD40. These three crystals structures 1) identify the conformational CD40 epitope for ABBV-323 recognition 2) illustrate conformational changes which occur in the CDRs of ABBV-323 Fab upon CD40 binding and 3) develop a structural hypothesis for an agonist/antagonist switch in the LCDR1 of this proprietary class of CD40 antibodies.
conclusionsThe structure of ABBV-323 Fab demonstrates a unique method for antagonism by stabilizing the proposed functional antiparallel dimer for CD40 receptor via novel contacts to LCDR1, namely residue position R32 which is further supported by a closely related agonist antibody FAB516 which shows only monomeric recognition and no contacts with LCDR1 due to a mutation to L32 on LCDR1. These data provide a structural basis for the full antagonist activity of ABBV-323.
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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.