[HTML][HTML] The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes
S Dong, KJ Hiam-Galvez, CT Mowery, KC Herold… - JCI insight, 2021 - ncbi.nlm.nih.gov
JCI insight, 2021•ncbi.nlm.nih.gov
BACKGROUND A previous phase I study showed that the infusion of autologous Tregs
expanded ex vivo into patients with recent-onset type 1 diabetes (T1D) had an excellent
safety profile. However, the majority of the infused Tregs were undetectable in the peripheral
blood 3 months postinfusion (Treg-T1D trial). Therefore, we conducted a phase I study (TILT
trial) combining polyclonal Tregs and low-dose IL-2, shown to enhance Treg survival and
expansion, and assessed the impact over time on Treg populations and other immune cells …
expanded ex vivo into patients with recent-onset type 1 diabetes (T1D) had an excellent
safety profile. However, the majority of the infused Tregs were undetectable in the peripheral
blood 3 months postinfusion (Treg-T1D trial). Therefore, we conducted a phase I study (TILT
trial) combining polyclonal Tregs and low-dose IL-2, shown to enhance Treg survival and
expansion, and assessed the impact over time on Treg populations and other immune cells …
Abstract
BACKGROUND
A previous phase I study showed that the infusion of autologous Tregs expanded ex vivo into patients with recent-onset type 1 diabetes (T1D) had an excellent safety profile. However, the majority of the infused Tregs were undetectable in the peripheral blood 3 months postinfusion (Treg-T1D trial). Therefore, we conducted a phase I study (TILT trial) combining polyclonal Tregs and low-dose IL-2, shown to enhance Treg survival and expansion, and assessed the impact over time on Treg populations and other immune cells.
METHODS
Patients with T1D were treated with a single infusion of autologous polyclonal Tregs followed by one or two 5-day courses of recombinant human low-dose IL-2 (ld-IL-2). Flow cytometry, cytometry by time of flight, and 10x Genomics single-cell RNA-Seq were used to follow the distinct immune cell populations’ phenotypes over time.
RESULTS
Multiparametric analysis revealed that the combination therapy led to an increase in the number of infused and endogenous Tregs but also resulted in a substantial increase from baseline in a subset of activated NK, mucosal associated invariant T, and clonal CD8+ T cell populations.
CONCLUSION
These data support the hypothesis that ld-IL-2 expands exogenously administered Tregs but also can expand cytotoxic cells. These results have important implications for the use of a combination of ld-IL-2 and Tregs for the treatment of autoimmune diseases with preexisting active immunity.
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