A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice
| Autor: | Philip Bernstein, Matthias von Herrath, Clive Wasserfall, Teodora Staeva, Philippe P. Pagni, Yulia Manenkova, Kevan C. Herold, Laura Straub, Mario R. Ehlers, Amira Bel Hani, Amanda L. Posgai, Ronald G. Gill, Tinalyn Kupfer, Songyan Deng, Mark A. Atkinson, Gerald T. Nepom |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Biomedical Research CD3 Complex Recombinant Fusion Proteins Endocrinology Diabetes and Metabolism medicine.medical_treatment Interleukin-1beta Pilot Projects Disease Drug Administration Schedule Autoimmune Diseases Immune tolerance Immunoglobulin Fab Fragments 03 medical and health sciences Mice Inbred NOD Insulin-Secreting Cells Internal medicine Insulin Secretion Internal Medicine Animals Insulin Multicenter Studies as Topic Medicine Prospective cohort study NOD mice Receptors Interleukin-1 Type I Type 1 diabetes business.industry Antibodies Monoclonal Reproducibility of Results Immunotherapy medicine.disease United States Specific Pathogen-Free Organisms 3. Good health Blockade Clinical trial Diabetes Mellitus Type 1 030104 developmental biology Research Design Immunology Drug Therapy Combination Female Interleukin-1 Receptor Accessory Protein business |
| Zdroj: | Diabetes. 65:1310-1316 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db15-0492 |
| Popis: | There is an ongoing need to develop strategic combinations of therapeutic agents to prevent type 1 diabetes (T1D) or to preserve islet β-cell mass in new-onset disease. Although clinical trials using candidate therapeutics are commonly based on preclinical studies, concern is growing regarding the reproducibility as well as the potential clinical translation of reported results using animal models of human disorders. In response, the National Institutes of Health Immune Tolerance Network and JDRF established a multicenter consortium of academic institutions designed to assess the efficacy and intergroup reproducibility of clinically applicable immunotherapies for reversing new-onset disease in the NOD mouse model of T1D. Predicated on prior studies, this consortium conducted coordinated, prospective studies, using joint standard operating procedures, fixed criteria for study entry, and common reagents, to optimize combined anti-CD3 treatment plus interleukin-1 (IL-1) blockade to reverse new-onset disease in NOD mice. We did not find that IL-1 blockade with anti–IL-1β monoclonal antibody or IL-1trap provided additional benefit for reversing new-onset disease compared with anti-CD3 treatment alone. These results demonstrate the value of larger, multicenter preclinical studies for vetting and prioritizing therapeutics for future clinical use. |
| Databáze: | OpenAIRE |
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