ArticleDiabetes2021
Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04279613 (A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 Administered Subcutaneously to Patients With Type 1 Diabetes Mellitus), which is not on this map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Multiple Ascending Dose Trial Investigating Safety, Tolerability and Pharmacokinetics of NNC0361-0041 Administered Subcutaneously to Patients With Type 1 Diabetes Mellitus
Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Trial
- A Tolerogenic Plasmid Inhibits Autoantibody Production Triggered by Immunization With Human Peptidyl Arginine Deiminase 4.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Review
- Antigen-specific immunotherapies for autoimmune disease.Nature reviews. Rheumatology · 2025Review
- Cytokine Couture: Designer IL2 Molecules for the Treatment of Disease.ImmunoTargets and therapy · 2025Review
- Advances in molecular adjuvants for nucleic acid vaccines.Frontiers in immunology · 2025Review
- Method for plasmid-based antibiotic-free fermentation.Microbial cell factories · 2024Article
- A comprehensive overview of tolerogenic vaccine adjuvants and their modes of action.Frontiers in immunology · 2024Review
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- "IL-2 immunotherapy for targeting regulatory T cells in autoimmunity".Genes and immunity · 2023Review
- Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Delivery route considerations for designing antigen-specific biomaterial strategies to combat autoimmunity.Advanced nanobiomed research · 2023Article
- Tolerogenic Immune-Modifying Nanoparticles Encapsulating Multiple Recombinant Pancreatic β Cell Proteins Prevent Onset and Progression of Type 1 Diabetes in Nonobese Diabetic Mice.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Preclinical evaluation of a precision medicine approach to DNA vaccination in type 1 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes is an autoimmune disease in which insulin-secreting β-cells are destroyed, leading to a life-long dependency on exogenous insulin. There are no approved disease-modifying therapies available, and future immunotherapies would need to avoid generalized immune suppression. We developed a novel plasmid expressing preproinsulin2 and a combination of immune-modulatory cytokines (transforming growth factor-beta-1, interleukin [IL] 10 and IL-2) capable of near-complete prevention of autoimmune diabetes in non-obese diabetic mice. Efficacy depended on preproinsulin2, suggesting antigen-specific tolerization, and on the cytokine combination encoded. Diabetes suppression was achieved following either intramuscular or subcutaneous injections. Intramuscular plasmid treatment promoted increased peripheral levels of endogenous IL-10 and modulated myeloid cell types without inducing global immunosuppression. To prepare for first-in-human studies, the plasmid was modified to allow for selection without the use of antibiotic resistance; this modification had no impact on efficacy. This pre-clinical study demonstrates that this multi-component, plasmid-based antigen-specific immunotherapy holds potential for inducing self-tolerance in persons at risk of developing type 1 diabetes. Importantly, the study also informs on relevant cytokine and immune cell biomarkers that may facilitate clinical trials. This therapy is currently being tested for safety and tolerability in a phase 1 trial (ClinicalTrials.gov Identifier: NCT04279613).
Identifiers
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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.