Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis.
OBJECTIVE
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, 3×106or 10×106tolDC 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 10×106tolDC; 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.


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


BACKGROUND
NCT01352858.
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
G M
GM
Bell
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
A E
AE
Anderson
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
J
J
Diboll
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
R
R
Reece
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
O
O
Eltherington
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
R A
RA
Harry
Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
T
T
Fouweather
Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
C
C
MacDonald
Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
T
T
Chadwick
Institute of Health and Society, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.|Clinical Trials Unit, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
E
E
McColl
Haematological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
J
J
Dunn
Haematological Sciences, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
A M
AM
Dickinson
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
C M U
CM
Hilkens
Arthritis Research UK Rheumatoid Arthritis Pathogenesis Centre of Excellence (RACE), Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle upon Tyne, UK.
John D
JD
Isaacs
D000328:Adult; D000368:Aged; D015535:Arthritis, Psoriatic / Q000276:immunology / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001182:Arthroscopy / Q000379:methods; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007719:Knee Joint; D008297:Male; D008875:Middle Aged; D010342:Patient Acceptance of Health Care; D012720:Severity of Illness Index; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
Inflammation; Rheumatoid Arthritis; Synovial fluid; Treatment