Article Text

Tolerising cellular therapies: what is their promise for autoimmune disease?
  1. Chijioke H Mosanya1,2,
  2. John D Isaacs1,2
  1. 1 Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  2. 2 Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
  1. Correspondence to John D Isaacs, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle upon Tyne NE2 4HH, UK; john.isaacs{at}ncl.ac.uk

Abstract

The current management of autoimmunity involves the administration of immunosuppressive drugs coupled to symptomatic and functional interventions such as anti-inflammatory therapies and hormone replacement. Given the chronic nature of autoimmunity, however, the ideal therapeutic strategy would be to reinduce self-tolerance before significant tissue damage has accrued. Defects in, or defective regulation of, key immune cells such as regulatory T cells have been documented in several types of human autoimmunity. Consequently, it has been suggested that the administration of ex vivo generated, tolerogenic immune cell populations could provide a tractable therapeutic strategy. Several potentially tolerogenic cellular therapies have been developed in recent years; concurrent advances in cell manufacturing technologies promise scalable, affordable interventions if safety and efficacy can be demonstrated. These therapies include mesenchymal stromal cells, tolerogenic dendritic cells and regulatory T cells. Each has advantages and disadvantages, particularly in terms of the requirement for a bespoke versus an ‘off-the-shelf’ treatment but also their suitability in particular clinical scenarios. In this review, we examine the current evidence for these three types of cellular therapy, in the context of a broader discussion around potential development pathway(s) and their likely future role. A brief overview of preclinical data is followed by a comprehensive discussion of human data.

  • Cellular therapies
  • tolerogenic dendritic cells
  • regulatory T-cells
  • mesenchymal stromal cells
  • TR1 cells
  • rheumatoid arthritis
  • type 1 diabetes
  • Crohn’s disease
  • multiple sclerosis
  • systemic lupus erythematosus
  • graft versus host disease
  • autoimmune thyroiditis
  • myasthenia gravis

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors The outline of the article was developed by JDI and CHM. The first draft of the article was prepared by CHM. Subsequent drafts were prepared by CHM following suggestions and amendments by JDI. Figures and tables were prepared by CHM and approved by JDI. Both authors approved the final submitted article and its revision in response to Reviewers' comments.

  • Funding This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The authors’ work is supported by the Arthritis Research UK (ARUK)-Newcastle Biomedicine Experimental Arthritis Treatment Centre, the ARUK Centre of Excellence in RA Pathogenesis and by the European Commission Innovative Medicines Initiative Rheuma-Tolerance for Cure (RT-CURE).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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