SRA

Background: A previous Phase I study showed that the infusion of autologous Treg cells expanded ex-vivo into recent onset Type 1 Diabetes (T1D) patients had an excellent safety profile, however, the majority of the infused Tregs could no longer be detected in the peripheral blood three months post-infusion (NCT01210664-Treg-T1D Trial). Interleukin-2 (IL-2) is a well-characterized cytokine that has been shown to enhance human Treg cell survival and expansion at low doses in vivo. Therefore, a Phase 1 study (NCT02772679-TILT trial) was conducted combining a single infusion of autologous polyclonal Tregs, expanded ex vivo, followed by one or two 5-day courses of recombinant human low dose IL-2 (ld-IL-2) at 0.3 x 10^6 to 1 x 10^6 units/dose. The infusions had an acceptable safety profile, but all 9 patients failed to maintain C-peptide production at pre-treatment levels. Results: Single cell gene expression analysis revealed that the combination therapy led to a transient increase in the number of infused and endogenous Tregs but also resulted in a significant increase from baseline in a subset of activated NK, Mucosal-associated invariant T (MAIT) and clonal CD8+ T populations from populations Overall design: CD45+ cells were isolated by FACS, combined into 30 pools and sequenced into three distinct batches. The data from each time point of each patient's sample was then deconvoluted using the Demuxlet computational package. The gene expression profile and TCR sequencing of more than 400,000 cells was analyzed Each sequenced sample is a mix of several patients and timepoints.