Clinical Use of Tolerogenic Dendritic Cells-Harmonization Approach in European Collaborative Effort

Table 1

Completed phase 1 safety studies using tolerance-inducing DC.

Group	Indication	Cell culture conditions	Antigen (Ag)	Treatment regimen	Route of administration	Outcomes	Ref.
Giannoukakis, Trucco; Pittsburgh, USA	Type 1 diabetes	Use of antisense ODN targeting CD40, CD80, and CD86 in mo-DC	No Ag	4 injections of 1 × 10^7 cells every two weeks	Intradermal	(i) No AE; (ii) No clinical effect; (iii) Treatment-associated increase of B220+ CD11c+ B cells; (iv) Evidence for reactivation of C-peptide in subjects that were C-peptide negative	[12]
Thomas; Brisbane, Australia	RA	Addition of Bay11-7082 to mo-DC cultures	Citrullinated peptides: collagen type -Cit1240, fibrinogen chain-Cit720, fibrinogen chain-Cit436, and vimentin-Cit450	1 injection of low-dose (0.5–1 × 10^6 cells) or high-dose (2–4.5 × 10^6 cells)	Intradermal	(i) Grade 1 AE (injection site reactions, transient leucopenia, and headache); (ii) No induction of disease flares and reduction of DAS28 in treated patients; (iii) Systemic anti-inflammatory effect based on CRP levels, reduced frequency of Teff, and proinflammatory cytokines and chemokines in treated patients	[10]
Panes, Benitez-Ribas, and Ricart; Barcelona, Spain	Crohn’s disease	Addition of dexamethasone and vitamin A to mo-DC cultures	No Ag	Dose-escalation study: a single or 3 consecutive injections at 2-week intervals of 2 × 10^6, 5 × 10^6, and 10 × 10^6 cells	Intraperitoneal	(i) No AE (3 patients withdrew because of worsening of disease symptoms); (ii) Clinical improvement in 3 out of 13 patients (1 clinical remission, 2 clinical responses); (iii) Increase of circulating Treg and decrease in IFN- levels	[11]
Hilkens, Isaacs; Newcastle upon Tyne, UK	Inflammatory arthritis	Addition of dexamethasone and vitamin D to mo-DC cultures	Autologous synovial fluid	Dose-escalation study: a single injection of 1 × 10^6, 3 × 10^6, and 10 × 10^6 cells	Intra-articular	(i) No evidence of acute toxicity; (ii) Treatment acceptable to patients
Joo, Bae; Seoul, South Korea	RA	CreaVax-RA (autologous tolerogenic DC)	recombinant PAD4, RA33, citrullinated-filaggrin and vimentin	5 injections of low-dose (0.5 × 10^7 cells) and high-dose (1.5 × 10^7)	Not indicated	(i) Treatment was well tolerated; (ii) Antigen-specific autoantibodies decreased in 5/9 autoantibody-pos. patients	[34]