Type 1 diabetes immunotherapy using polyclonal regulatory T cells

• Published in: Science translational medicine Vol. 7; no. 315; p. 315ra189
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States 25.11.2015
• Subjects: Adult; Diabetes Mellitus, Type 1 - therapy; Female; Humans; Immunotherapy; Male; T-Lymphocytes, Regulatory - immunology; Young Adult
• ISSN: 1946-6242
• DOI: 10.1126/scitranslmed.aad4134

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.