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Characterization and Expansion of Autologous GMP-ready Regulatory T Cells for TREG-based Cell Therapy in Patients with Ulcerative Colitis
- Source :
- Inflammatory bowel diseases. 23(8)
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Adult
Male
Adoptive cell transfer
Cell- and Tissue-Based Therapy
Inflammation
T-Lymphocytes, Regulatory
Cell therapy
03 medical and health sciences
0302 clinical medicine
T-Lymphocyte Subsets
Immunology and Allergy
Medicine
Humans
IL-2 receptor
Colitis
Cells, Cultured
Aged
business.industry
Gastroenterology
FOXP3
Middle Aged
medicine.disease
Adoptive Transfer
030104 developmental biology
Immunology
Colitis, Ulcerative
Female
medicine.symptom
business
Ex vivo
CD8
030215 immunology
Subjects
Details
- ISSN :
- 15364844
- Volume :
- 23
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Inflammatory bowel diseases
- Accession number :
- edsair.doi.dedup.....763b73413977e202005402275ee147e4