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10X genomics single cell GEX and VDJ 5' sequencing of PBMC from Type 1 Diabetes patients treated with Treg therapy alone or plus low dose IL-2

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE178991 | GEO | 2021/09/25

REPOSITORIES: GEO

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