A robust, good manufacturing practice–compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy

Abdullah Alsuliman, Stanley H. Appel, David R. Beers, Rafet Basar, Hila Shaim, Indresh Kaur, Jane Zulovich, Eric Yvon, Muharrem Muftuoglu, Nobuhiko Imahashi, Kayo Kondo, Enli Liu, Elizabeth J. Shpall, Katayoun Rezvani

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1312-1324
Number of pages13
JournalCytotherapy
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • amyotrophic lateral sclerosis
  • good manufacturing practice
  • rapamycin
  • regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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