title: A robust, good manufacturing practice-compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy.
abstract: Regulatory T cells (Tregs) play a fundamental role in the maintenance of self-tolerance and immune homeostasis. Defects in Treg function and/or frequencies have been reported in multiple disease models. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Compelling evidence supports a neuroprotective role for Tregs in this disease. Indeed, rapid progression in ALS patients is associated with decreased FoxP3 expression and Treg frequencies. Thus, we propose that strategies to restore Treg number and function may slow disease progression in ALS. In this study, we developed a robust, Good Manufacturing Practice (GMP)-compliant procedure to enrich and expand Tregs from ALS patients. Tregs isolated from these patients were phenotypically similar to those from healthy individuals but were impaired in their ability to suppress T-cell effector function. In vitro expansion of Tregs for 4 weeks in the presence of GMP-grade anti-CD3/CD28 beads, interleukin (IL)-2 and rapamcyin resulted in a 25- to 200-fold increase in their number and restored their immunoregulatory activity. Collectively, our data facilitate and support the implementation of clinical trials of adoptive therapy with ex vivo expanded and highly suppressive Tregs in patients with ALS.
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA; Stem Cell & Tissue Re-engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors: Abdullah
authors: A
authors: Alsuliman
authors: Peggy and Gary Edwards ALS Laboratory, Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas, USA.
authors: Stanley H
authors: SH
authors: Appel
authors: Peggy and Gary Edwards ALS Laboratory, Department of Neurology, Houston Methodist Neurological Institute, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, Texas, USA.
authors: David R
authors: DR
authors: Beers
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Rafet
authors: R
authors: Basar
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Hila
authors: H
authors: Shaim
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Indresh
authors: I
authors: Kaur
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Jane
authors: J
authors: Zulovich
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Eric
authors: E
authors: Yvon
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Muharrem
authors: M
authors: Muftuoglu
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Nobuhiko
authors: N
authors: Imahashi
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Kayo
authors: K
authors: Kondo
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Enli
authors: E
authors: Liu
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA.
authors: Elizabeth J
authors: EJ
authors: Shpall
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: KRezvani@mdanderson.org.
authors: Katayoun
authors: K
authors: Rezvani
mesh_terms: D019264:Adoptive Transfer / Q000379:methods / Q000592:standards*; D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002469:Cell Separation / Q000379:methods / Q000592:standards; D064987:Cell- and Tissue-Based Therapy / Q000379:methods / Q000592:standards*; D002478:Cells, Cultured; D019983:Guideline Adherence / Q000592:standards; D006801:Humans; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000378:metabolism; D061251:Primary Cell Culture / Q000379:methods / Q000592:standards; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*
chemical_list: D007376:Interleukin-2
keywords: amyotrophic lateral sclerosis; good manufacturing practice; rapamycin; regulatory T cells