ArticlePloS one2013
Transient B-cell depletion with anti-CD20 in combination with proinsulin DNA vaccine or oral insulin: immunologic effects and efficacy in NOD mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Oxidative stress-initiated one-carbon metabolism drives the generation of interleukin-10-producing B cells to resolve pneumonia.Cellular & molecular immunology · 2024Article
- 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
- Nanotechnology in Immunotherapy for Type 1 Diabetes: Promising Innovations and Future Advances.Pharmaceutics · 2022Review
- Type 1 diabetes mellitus and its oral tolerance therapy.World journal of diabetes · 2020Review
- Stimulator of interferon genes agonists attenuate type I diabetes progression in NOD mice.Immunology · 2019Article
- A multi-epitope DNA vaccine enables a broad engagement of diabetogenic T cells for tolerance in Type 1 diabetes.Journal of autoimmunity · 2019Article
- The challenge of modulating β-cell autoimmunity in type 1 diabetes.The lancet. Diabetes & endocrinology · 2019Review
- B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model.Diabetologia · 2018Article
- Gut microbiota utilize immunoglobulin A for mucosal colonization.Science (New York, N.Y.) · 2018Article
- Antigen-specific immunotherapies in rheumatic diseases.Nature reviews. Rheumatology · 2017Review
- Anti-CD137 enhances anti-CD20 therapy of systemic B-cell lymphoma with altered immune homeostasis but negligible toxicity.Oncoimmunology · 2016Article
- Report from IPITA-TTS Opinion Leaders Meeting on the Future of β-Cell Replacement.Transplantation · 2016Article
- Immune interventions to preserve β cell function in type 1 diabetes.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2016Review
- Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets.F1000Research · 2016Review
- T regulatory cells and B cells cooperate to form a regulatory loop that maintains gut homeostasis and suppresses dextran sulfate sodium-induced colitis.Mucosal immunology · 2015Article
- The microRNA-212/132 cluster regulates B cell development by targeting Sox4.The Journal of experimental medicine · 2015Article
- Antigen-Specific Regulatory T Cells and Low Dose of IL-2 in Treatment of Type 1 Diabetes.Frontiers in immunology · 2015Review
- Targeted immune interventions for type 1 diabetes: not as easy as it looks!Current opinion in endocrinology, diabetes, and obesity · 2014Review
- Restoring the balance: immunotherapeutic combinations for autoimmune disease.Disease models & mechanisms · 2014Review
- Anti-CD20 as the B-Cell Targeting Agent in a Combined Therapy to Modulate Anti-Factor VIII Immune Responses in Hemophilia a Inhibitor Mice.Frontiers in immunology · 2014Article
Corrections and comments
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Authors and funding
22 authors at 8 institutions in 1 country.
Funding
Abstract
A recent type 1 diabetes (T1D) clinical trial of rituximab (a B cell-depleting anti-CD20 antibody) achieved some therapeutic benefit in preserving C-peptide for a period of approximately nine months in patients with recently diagnosed diabetes. Our previous data in the NOD mouse demonstrated that co-administration of antigen (insulin) with anti-CD3 antibody (a T cell-directed immunomodulator) offers better protection than either entity alone, indicating that novel combination therapies that include a T1D-related autoantigen are possible. To accelerate the identification and development of novel combination therapies that can be advanced into the clinic, we have evaluated the combination of a mouse anti-CD20 antibody with either oral insulin or a proinsulin-expressing DNA vaccine. Anti-CD20 alone, given once or on 4 consecutive days, produced transient B cell depletion but did not prevent or reverse T1D in the NOD mouse. Oral insulin alone (twice weekly for 6 weeks) was also ineffective, while proinsulin DNA (weekly for up to 12 weeks) showed a trend toward modest efficacy. Combination of anti-CD20 with oral insulin was ineffective in reversing diabetes in NOD mice whose glycemia was controlled with SC insulin pellets; these experiments were performed in three independent labs. Combination of anti-CD20 with proinsulin DNA was also ineffective in diabetes reversal, but did show modest efficacy in diabetes prevention (p = 0.04). In the prevention studies, anti-CD20 plus proinsulin resulted in modest increases in Tregs in pancreatic lymph nodes and elevated levels of proinsulin-specific CD4+ T-cells that produced IL-4. Thus, combination therapy with anti-CD20 and either oral insulin or proinsulin does not protect hyperglycemic NOD mice, but the combination with proinsulin offers limited efficacy in T1D prevention, potentially by augmentation of proinsulin-specific IL-4 production.
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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.