You are here

Article Text

Article menu

Download PDFPDF

Basic and translational research
Extended report
Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis
  1. G M Bell1,
  2. A E Anderson1,
  3. J Diboll1,
  4. R Reece1,
  5. O Eltherington1,
  6. R A Harry1,
  7. T Fouweather2,
  8. C MacDonald2,
  9. T Chadwick2,
  10. E McColl2,3,
  11. J Dunn4,
  12. A M Dickinson4,
  13. C M U Hilkens1,
  14. John D Isaacs1
  1. 1Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK
  2. 2Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  3. 3Clinical Trials Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
  4. 4Haematological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK
  1. Correspondence to Professor JD Isaacs, Institute of Cellular Medicine, Faculty of Medical Sciences, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK; john.isaacs{at}newcastle.ac.uk

Abstract

Objectives To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities.

Methods An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood.

Results There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high.

Conclusion IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable.

Trial registration number NCT01352858.

  • Rheumatoid Arthritis
  • Treatment
  • Synovial fluid
  • Inflammation

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/annrheumdis-2015-208456

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Handling editor Tore K Kvien

    • GMB and AEA are joint first authors.

    • Contributors GMB, AEA, JD, RR, OE, RAH and JD carried out the study; JDI and CMUH conceived and designed the study; TF and TC performed statistical analysis; CMD and MEMC oversaw the clinical trial; AMD supervised the good manufacturing practice production process; JDI supervised the study and drafted the manuscript; GMB, AEA, JD, OE, RAH and CMUH contributed to drafting the manuscript; all authors provided feedback on the manuscript.

    • Funding This work was funded by Arthritis Research UK grant 18155. Research within the Musculoskeletal Research Group is supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. CMUH and JDI have received support from the European Cooperation for Science and Technology Action to Focus and Accelerate Cellular Tolerance-inducing Therapies (A FACTT; BM1305; http://www.afactt.eu).

    • Competing interests None declared.

    • Ethics approval National Research Ethics Service Committee North East (Sunderland).

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