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Type 1 diabetes immunotherapy using polyclonal regulatory T cells.

  • Author(s): Bluestone, Jeffrey A
  • Buckner, Jane H
  • Fitch, Mark
  • Gitelman, Stephen E
  • Gupta, Shipra
  • Hellerstein, Marc K
  • Herold, Kevan C
  • Lares, Angela
  • Lee, Michael R
  • Li, Kelvin
  • Liu, Weihong
  • Long, S Alice
  • Masiello, Lisa M
  • Nguyen, Vinh
  • Putnam, Amy L
  • Rieck, Mary
  • Sayre, Peter H
  • Tang, Qizhi
  • et al.

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.

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