دورية أكاديمية
Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes.
| العنوان: | Multicomponent Plasmid Protects Mice From Spontaneous Autoimmune Diabetes. |
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| المؤلفون: | Pagni PP; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Chaplin J; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Wijaranakula M; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Wesley JD; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Granger J; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Cracraft J; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., O'Brien C; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Perdue N; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Kumar V; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Li S; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Ratliff SS; La Jolla Institute for Immunology, La Jolla, CA, USA., Roach A; Type 1 Diabetes & Kidney Disease, Global Drug Discovery, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Misquith A; Discovery Biologics, Global Research Technologies, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Chan CL; Discovery Biologics, Global Research Technologies, Novo Nordisk Research Center Seattle, Inc., Seattle, WA, U.S.A., Coppieters K; Project and Alliance Management, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark., von Herrath M; La Jolla Institute for Immunology, La Jolla, CA, USA matthias@lji.org.; Global Chief Medical Office, Novo Nordisk A/S, Søborg, Denmark. |
| المصدر: | Diabetes [Diabetes] 2021 Aug 13. Date of Electronic Publication: 2021 Aug 13. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مستخلص: | 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). (© 2021 by the American Diabetes Association.) |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT04279613 |
| تواريخ الأحداث: | Date Created: 20210814 Latest Revision: 20240402 |
| رمز التحديث: | 20240402 |
| مُعرف محوري في PubMed: | PMC8763876 |
| DOI: | 10.2337/db21-0327 |
| PMID: | 34389610 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db21-0327 |