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Type 1 diabetes immunotherapy using polyclonal regulatory T cells

  • Author(s): Bluestone, JA
  • Buckner, JH
  • Fitch, M
  • Gitelman, SE
  • Gupta, S
  • Hellerstein, MK
  • Herold, KC
  • Lares, A
  • Lee, MR
  • Li, K
  • Liu, W
  • Long, SA
  • Masiello, LM
  • Nguyen, V
  • Putnam, AL
  • Rieck, M
  • Sayre, PH
  • Tang, Q
  • et al.
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+CD127lo/-CD25+ polyclonal Tregs (0.05 × 108 to 26 × 108 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+CD25hiCD127lo 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.

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