Type 1 diabetes immunotherapy using polyclonal regulatory T cells
Jeffrey A Bluestone, Jane H Buckner, Mark Fitch, Stephen E Gitelman, Shipra Gupta, Marc K Hellerstein, Kevan C Herold, Angela Lares, Michael R Lee, Kelvin Li, Weihong Liu, S Alice Long, Lisa M Masiello, Vinh Nguyen, Amy L Putnam, Mary Rieck, Peter H Sayre, Qizhi Tang, Jeffrey A Bluestone, Jane H Buckner, Mark Fitch, Stephen E Gitelman, Shipra Gupta, Marc K Hellerstein, Kevan C Herold, Angela Lares, Michael R Lee, Kelvin Li, Weihong Liu, S Alice Long, Lisa M Masiello, Vinh Nguyen, Amy L Putnam, Mary Rieck, Peter H Sayre, Qizhi Tang
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.
Conflict of interest statement
Competing interests: J.A.B, A.L.P., W.L., and Z.T. are co-inventors on patents (US 20080131445 A1 and US 7722862 B2) filed in connection with the manufacturing of the Treg product. J.A.B. and Q.T. have received funding from Caladrius Biosciences and other in-kind contributions form BD Biosciences. The remaining authors declare that they have no competing interests.
Copyright © 2015, American Association for the Advancement of Science.
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Source: PubMed