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| Status |
Public on Apr 15, 2024 |
| Title |
Maintenance of beta cell function in adolescent T1D subjects treated with a single dose of polyclonal expanded Treg is linked to lower ex vivo Treg expansion |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Adoptive transfer of CD4+CD25hiCD127low FOXP3+ regulatory T cells (Treg) improves outcome as an adjunct treatment in transplantation to maintain tolerance. Phase I clinical trials have shown safety in adults, however, adoptive Treg tolerance is poorly understood in autoimmunity. Here, we explore factors contributing to efficacy in an autologous polyclonal expanded Treg (expTregs) Phase 2 clinical trial in 107 adolescents with recent-onset T1D (Sanford/Lisata Therapeutics Trex Phase 2 clinical trial) randomized 1:1:1 high and low treatment to placebo. A single dose of expTreg therapy (1-24x106cells/kg) did not prevent the decline in the residual beta cell function over two years compared to placebo (p=0.39), regardless of age, baseline c-peptide, or dose of expTreg (p=0.27). expTregs were a highly activated, pure, and suppressive Treg population as determined using flow cytometry and bulk RNA-seq prior to adoptive transfer. A transient increase of activated memory Tregs was detectable by flow cytometry and single-cell RNA-seq one week after infusion in the high dose cohort (p=0.003), suggesting effective transfer of expTreg. However, lower in vitro fold expansion and its linked gene signature associated with better outcome regardless of Treg dose. Together, these results suggest that expTregs quantity alone does not alter outcome; instead, expTreg quality, likely influenced by endogenous Treg features, may be important factors contributing to the efficacy of this treatment in preventing T1D progression.
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| Overall design |
These data contain 10x Gene Expression and Feature Barcode (CITE-seq) data from Bronchial Alveolar Lavage samples from twelve samples taken from eight intubated patients at two timepoints. Each bam file corresponds to a single sample from a single patient at a timepoints (denoted v1 or v2 for time). Four patients were suffering from Acute Respiratory Distress Syndrom (ARDS) at time of first sample (SLK3, SLK7, SLK22, SLK23).
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| Contributor(s) |
Bender C, Wiedeman A, Hu A, Ylescupidez A, Gitelman S, Sietsema WK, Griffen K, Long SA |
| Citation(s) |
38718135 |
| |
| Submission date |
Sep 14, 2023 |
| Last update date |
Jul 15, 2024 |
| Contact name |
Stephanie Osmond |
| E-mail(s) |
sosmond@benaroyaresearch.org
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| Organization name |
Benaroya Research Institute
|
| Street address |
1201 9th Ave
|
| City |
Seattle, |
| State/province |
WA |
| ZIP/Postal code |
98101 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE243278 |
A phase II randomized trial with autologous polyclonal expanded regulatory T cells in children with new-onset type 1 diabetes |
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| Relations |
| BioProject |
PRJNA1017390 |
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