Table 3

Clinical trials of TolDC in autoimmune disorders

Diseases and clinical trialsNumber of patients, source of cells, dose and route of administrationOutcomesComments
Diabetes mellitus
 1. Giannoukakis et al (2011)101
 A randomised double-blind phase I study
10 patients with type 1 diabetes received 10×106 autologous peripheral blood-derived dendritic cells intradermally every 2 weeks for 4 administrations (7 received ex vivo manipulated DC lacking CD80/CD86 while 3 controls received non-manipulated immature DCs).Safely tolerated. Significant increase in the proportion of B220+ CD11c- B cells, mainly in patients that received manipulated dendritic cells. Detectable C-peptide in patients that had undetectable pretreatment C-peptide.First use of tolerogenic dendritic cells in human autoimmunity.
Crohn’s disease
 2. Jauregui-Amezaga et al (2015)102
 Phase I dose escalation study
9 patients with refractory Crohn’s disease received autologous monocyte-derived tolDC via sonography-guided intraperitoneal injections in six cohorts: a one-time injection of 2×106/5×106/10×106 cells for the first 3 cohorts and three biweekly intraperitoneal injections at same escalating doses for another three cohorts.No adverse effects were detected during tolDC injection or follow-up. Some anecdotal efficacy was observed and one patient achieved remission.TolDC were not loaded with specific antigens. Three patients withdrew due to worsening symptoms.
Rheumatoid and inflammatory arthritis
 3. Benham et al (2015)104
 Phase I randomised controlled study
34 patients with RA carrying HLA-DRB1 ‘shared epitope’ allele. 18 received autologous monocyte-derived tolDC intradermally at a dose of between 0.6 to 4.5×106 cells (depending on yield) while 16 were controlsWell tolerated. Low grade adverse events including transient leucopoenia, anaemia and transaminitis. Treatment was associated with reduction in effector T cells and an increased regulatory:effector T cell ratio.First use of dendritic cells for treatment of RA. TolDC were exposed to citrullinated peptides to confer antigen specificity
 4. Bell et al (2016)103
 Phase I unblinded randomised controlled dose escalation study
Monocyte-derived autologous tolDC. Three cohorts of patients with rheumatoid or other inflammatory arthritis received 1×106, 3×106, or 10×106 cells into an inflamed knee. DC exposed to synovial fluid during culture as a source of auto-antigen. A fourth (control) cohort received arthroscopic washout alone.Safe and acceptable procedure, feasible to manufacture tolDC from peripheral blood of patients with arthritis. Arthroscopically assessed synovial vascularity and synovitis improved in some patients who received TolDC.First intra-articular administration of tolDC. No consistent immunomodulatory trend in peripheral blood between treatment and control groups. No evidence for DC-induced joint flare (indicating DC stability).
  • TolDC, tolerogenic dendritic cells.