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Diabetes. 2016 May;65(5):1310-6. doi: 10.2337/db15-0492. Epub 2015 Dec 30.

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.

Author information

1
Departments of Surgery and Immunology, University of Colorado Denver, Aurora, CO ronald.gill@ucdenver.edu.
2
La Jolla Institute for Allergy and Immunology, La Jolla, CA.
3
Departments of Surgery and Immunology, University of Colorado Denver, Aurora, CO.
4
Department of Pathology, University of Florida, Gainesville, FL.
5
Yale University School of Medicine, New Haven, CT.
6
Immune Tolerance Network, University of California, San Francisco, San Francisco, CA.
7
Immune Tolerance Network, Bethesda, MD.
8
JDRF, New York, NY.
9
Benaroya Research Institute, Seattle, WA.

Abstract

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.

Comment in

PMID:
26718498
PMCID:
PMC5860426
DOI:
10.2337/db15-0492
[Indexed for MEDLINE]
Free PMC Article

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