In the publication of the authors describe a phase 1b clinical trial to investigate the safety and feasibility of tolDC therapy for the CNS-related autoimmune disorders Multiple Sclerosis and Neuromyelitis optica with peptide-loaded tolerogenic dendritic cells.
Autologous tolerogenic dendritic cells have been generated from patients PBMCS under GMP compliant conditions using the Lonza X-VIVO Medium.
Monocytes have cultured in In the protocol in the presence of 500 IU (international units)/mL of IL-4 and 800 IU/mL of GM-CSF during 7 d in X-VIVO-15 (BioWhittaker; Lonza) supplemented with 2% autologous serum.
At day 3, fresh medium and cytokines were added; furthermore, 10-6 M dexamethasone was added to the cells to induce the tolerogenic phenotype.
At day 6, to boost peptide-specific DC tolerogenic properties, cytokines including IL-1ß, IL-6, TNF-a, and prostaglandin E2, as well as the immunogenic peptides , were added for 24 h and washed before administration. TolDC from MS patients were loaded with seven myelin peptides and DC from NMOSD patients were stimulated with peptides from AQP4 patients.
Patients received intravenous administration of TolDC every two weeks (week 0 , 2 and 4 ) representing a total of three administrations per patient. The dose escalation (50 × 10exp6, 100 × 10exp6, 150 × 10exp6, and 300 × 10exp6 DCs) occured as expected in the absence of limiting toxicity in the previous dosage level.