Characterization and Expansion of Autologous GMP-ready Regulatory T Cells for TREG-based Cell Therapy in Patients with Ulcerative Colitis
BACKGROUND: A local imbalance between regulatory (Treg) and effector T cells is believed to play a major role in gut-specific inflammation, including ulcerative colitis (UC). Restoration of this balance through an adoptive Treg transfer is an attractive new treatment approach in patients who are refractory to current standard therapies. It was our goal to develop a Good Manufacturing Practices (GMP)-conform protocol for expansion of UC Treg cells as a rational backbone for future studies on Treg therapy in UC.
METHODS: CD25 blood T cells derived from patients with UC were ex vivo expanded in the presence of IL-2, rapamycin, and anti-CD3/anti-CD28 expander beads using a GMP-conform protocol. Cells were subsequently assessed for stability and function.
RESULTS: Patient-derived ex vivo rapamycin-expanded GMP-ready CD25 cells were polyclonal, hypomethylated at intron 1 of the FoxP3 locus, and suppressive in carboxyfluorescein succinimidyl ester-dilution assays against autologous peripheral blood-derived and allogeneic colon-derived responder cells. Function was mediated by soluble factors, including toxic granules. In addition to CD4 T cells, suppressive hypermethylated CD8 T-cell subsets were also induced during the expansion process.
CONCLUSIONS: Patient-derived rapamycin-expanded CD25 cells are stable and functional, and as such, ready to serve in a phase I dose-escalation safety study in UC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Inflammatory bowel diseases - 23(2017), 8 vom: 01. Aug., Seite 1348-1359 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Voskens, Caroline J [VerfasserIn] |
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| Anmerkungen: |
Date Completed 26.06.2018 Date Revised 13.09.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/MIB.0000000000001192 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM273845853 |
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| 245 | 1 | 0 | |a Characterization and Expansion of Autologous GMP-ready Regulatory T Cells for TREG-based Cell Therapy in Patients with Ulcerative Colitis |
| 264 | 1 | |c 2017 | |
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| 500 | |a Date Completed 26.06.2018 | ||
| 500 | |a Date Revised 13.09.2018 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: A local imbalance between regulatory (Treg) and effector T cells is believed to play a major role in gut-specific inflammation, including ulcerative colitis (UC). Restoration of this balance through an adoptive Treg transfer is an attractive new treatment approach in patients who are refractory to current standard therapies. It was our goal to develop a Good Manufacturing Practices (GMP)-conform protocol for expansion of UC Treg cells as a rational backbone for future studies on Treg therapy in UC | ||
| 520 | |a METHODS: CD25 blood T cells derived from patients with UC were ex vivo expanded in the presence of IL-2, rapamycin, and anti-CD3/anti-CD28 expander beads using a GMP-conform protocol. Cells were subsequently assessed for stability and function | ||
| 520 | |a RESULTS: Patient-derived ex vivo rapamycin-expanded GMP-ready CD25 cells were polyclonal, hypomethylated at intron 1 of the FoxP3 locus, and suppressive in carboxyfluorescein succinimidyl ester-dilution assays against autologous peripheral blood-derived and allogeneic colon-derived responder cells. Function was mediated by soluble factors, including toxic granules. In addition to CD4 T cells, suppressive hypermethylated CD8 T-cell subsets were also induced during the expansion process | ||
| 520 | |a CONCLUSIONS: Patient-derived rapamycin-expanded CD25 cells are stable and functional, and as such, ready to serve in a phase I dose-escalation safety study in UC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Fischer, Anika |e verfasserin |4 aut | |
| 700 | 1 | |a Roessner, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Lorenz, Carmen |e verfasserin |4 aut | |
| 700 | 1 | |a Hirschmann, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Atreya, Raja |e verfasserin |4 aut | |
| 700 | 1 | |a Neufert, Clemens |e verfasserin |4 aut | |
| 700 | 1 | |a Atreya, Imke |e verfasserin |4 aut | |
| 700 | 1 | |a Neurath, Markus F |e verfasserin |4 aut | |
| 700 | 1 | |a Schuler, Gerold |e verfasserin |4 aut | |
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