ArticleDiabetologia2014
A CD40-targeted peptide controls and reverses type 1 diabetes in NOD mice.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- The CD40-CD154 axis in transplantation: from immunobiology to therapeutic targeting.Frontiers in immunology · 2026Review
- A CD40-targeting peptide, OPT501, modulates inflammation in canine diabetes mellitus improving clinical outcomes.Frontiers in immunology · 2026Article
- Slow Subcutaneous Release of Glatiramer Acetate or CD40-Targeting Peptide KGYYNeurology international · 2024Article
- Factors Governing B Cell Recognition of Autoantigen and Function in Type 1 Diabetes.Antibodies (Basel, Switzerland) · 2024Review
- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
- Higher CD4Scientific reports · 2023Article
- Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS).Journal of neuroimmunology · 2023Article
- Canine diabetes mellitus demonstrates multiple markers of chronic inflammation including Th40 cell increases and elevated systemic-immune inflammation index, consistent with autoimmune dysregulation.Frontiers in immunology · 2023Article
- Transcriptional Regulation ofGenes · 2020Article
- CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis.Biomedicines · 2020Article
- CD40-targeting KGYYDiabetologia · 2019Article
- CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor. Reply to Pagni PP, Wolf A, Lo Conte M et al [letter].Diabetologia · 2019Article
- CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor.Diabetologia · 2019Article
- A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2019Article
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- Platelets in Skin Autoimmune Diseases.Frontiers in immunology · 2019Review
- Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40⁻CD154 Costimulatory Protein-Protein Interaction.Molecules (Basel, Switzerland) · 2018Article
- Bioconjugate Strategies for the Induction of Antigen-Specific Tolerance in Autoimmune Diseases.Bioconjugate chemistry · 2018Review
- Dichotomous roles of co-stimulatory molecules in diabetes mellitus.Oncotarget · 2018Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisThe CD40-CD154 interaction directs autoimmune inflammation. Therefore, a long-standing goal in the treatment of autoimmune disease has been to control the formation of that interaction and thereby prevent destructive inflammation. Antibodies blocking CD154 are successful in mouse models of autoimmune disease but, while promising when used in humans, unfortunate thrombotic events have occurred, forcing the termination of those studies.
methodsTo address the clinical problem of thrombotic events caused by anti-CD154 antibody treatment, we created a series of small peptides based on the CD154 domain that interacts with CD40 and tested the ability of these peptides to target CD40 and prevent type 1 diabetes in NOD mice.
resultsWe identified a lead candidate, the 15-mer KGYY15 peptide, which specifically targets CD40-positive cells in a size- and sequence-dependent manner. It is highly efficient in preventing hyperglycaemia in NOD mice that spontaneously develop type 1 diabetes. Importantly, KGYY15 can also reverse new-onset hyperglycaemia. KGYY15 is well tolerated and functions to control the cytokine profile of culprit Th40 effector T cells. The KGYY15 peptide is 87% homologous to the human sequence, suggesting that it is an important candidate for translational studies. CONCLUSIONS/
interpretationPeptide KGYY15 constitutes a viable therapeutic option to antibody therapy in targeting the CD40-CD154 interaction in type 1 diabetes. Given the involvement of CD40 in autoimmunity in general, it will also be important to evaluate KGYY15 in the treatment of other autoimmune diseases. This alternative therapeutic approach opens new avenues of exploration in targeting receptor-ligand interactions.
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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.