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Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.

Type 1 diabetes immunotherapy using polyclonal regulatory T cells.

Author information

1
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. jeff.bluestone@ucsf.edu.
2
Translational Research Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA.
3
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
4
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
5
Departments of Immunobiology and Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
6
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
7
KineMed Inc., Emeryville, CA 94608, USA.
8
Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
9
Division of Hematology-Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that occurs in genetically susceptible individuals. Regulatory T cells (Tregs) have been shown to be defective in the autoimmune disease setting. Thus, efforts to repair or replace Tregs in T1D may reverse autoimmunity and protect the remaining insulin-producing β cells. On the basis of this premise, a robust technique has been developed to isolate and expand Tregs from patients with T1D. The expanded Tregs retained their T cell receptor diversity and demonstrated enhanced functional activity. We report on a phase 1 trial to assess safety of Treg adoptive immunotherapy in T1D. Fourteen adult subjects with T1D, in four dosing cohorts, received ex vivo-expanded autologous CD4(+)CD127(lo/-)CD25(+) polyclonal Tregs (0.05 × 10(8) to 26 × 10(8) cells). A subset of the adoptively transferred Tregs was long-lived, with up to 25% of the peak level remaining in the circulation at 1 year after transfer. Immune studies showed transient increases in Tregs in recipients and retained a broad Treg FOXP3(+)CD4(+)CD25(hi)CD127(lo) phenotype long-term. There were no infusion reactions or cell therapy-related high-grade adverse events. C-peptide levels persisted out to 2+ years after transfer in several individuals. These results support the development of a phase 2 trial to test efficacy of the Treg therapy.

PMID:
26606968
PMCID:
PMC4729454
DOI:
10.1126/scitranslmed.aad4134
[Indexed for MEDLINE]
Free PMC Article

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