Phase I Clinical Trial of Islet Antigen–Specific Plasmid Coexpressing Tolerogenic Proteins Demonstrates Safety in Adults With Type 1 Diabetes
Antigen-specific therapy is needed to induce tolerance in type 1 diabetes at early disease stages or in combination with immunotherapy. We conducted a phase I trial in type 1 diabetes of a novel plasmid construct expressing the islet antigen preproinsulin (PPI) and immunomodulatory cytokines transforming growth factor-β1 (TGF-β1), interleukin-10 (IL-10), and IL-2. The therapy was safe and well tolerated. Dose-dependent changes in DNA plasmid levels and type 1 interferon signatures were detected; however, global and antigen-specific immune changes to PPI, IL-2, IL-10, or TGF-β1 were not observed. Further trials are needed to assess efficacy.
Authors
- Hanne Hastrup
- S. W. Lord
- M HALLER
- Kevan C. Herold (ORCID: https://orcid.org/0000-0003-1534-6613)
- Anna Kuś (ORCID: https://orcid.org/0000-0003-4520-6267)
- Karsten Wassermann
- JASON L. GAGLIA
- Priya Prahalad
- Carol L. Soppe (ORCID: https://orcid.org/0000-0002-8538-6314)
- Regine Bergholdt
- Darrell M. Wilson (ORCID: https://orcid.org/0000-0001-9589-6011)
- Robin Goland
- Mark A. Clements
- Todd M. Brusko
- Brian N Bundy
- Jennifer L Sherr
- Carla J Greenbaum
- Ingrid Libman
- Carmella Evans-Molina
- Sarah E Kobernat
- Matthias von Herrath
- Antoinette Moran
- William E Russell
- Philip Raskin
- S Alice Long
- Stephen E Gitelman
- Lin Wei Tung
- Mark Daniels
- Jeffrey P Krischer
- Type 1 Diabetes TrialNet Study Group*
Institutions
- Indiana University Health (US)
- Joslin Diabetes Center (US)
- University of Minnesota (US)
- Children's Hospital of Orange County (US)
- Children's Mercy Hospital (US)
- University of Pittsburgh (US)
- University of California, San Francisco (US)
- Novo Nordisk (Denmark) (DK)
- University of South Florida (US)
- Columbia University Irving Medical Center (US)
- Institute for Systems Biology (US)
- Yale University (US)
- University of Florida (US)
- Society of Interventional Radiology (US)
- Institute of Translational Health Sciences (US)
- MNGI Digestive Health (US)
- Urology of Indiana (US)
- Stanford Medicine (US)
- Indiana University – Purdue University Indianapolis (US)
- University of San Francisco (US)
- Columbia University (US)
- The University of Texas Southwestern Medical Center (US)
- Vanderbilt University Medical Center (US)
- University of Colorado Denver (US)
- Florida College (US)
- Stanford University (US)
Publication Details
- Journal
- Diabetes
- Published
- 2026-01-21
- DOI
- https://doi.org/10.2337/db25-0777
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00