Th181 - Safety and Feasibility of Intradermal and Intranodal Administration of Vitamin d3-tolerogenic Dendritic Cells in Two Coordinated Phase I Clinical Trials in Active Multiple Sclerosis Patients

Nathalie Cools; Barbara Willekens; Silvia Presas-Rodríguez; Anja ten Brinke; Catharina Gross; Maria Jose Mansilla – Instituto De Investigación Germans Trias I Pujol; Aina Teniente-Serra; Inez Wens; Thibo Billiet; Andreas Schulte-Mecklenbeck; Judith Derdelinckx; Daniela diblasi; Virginia Palomares-Cabeza; Annemie Ribbens; Wim Van Hecke; Ana Maria Barriocanal; Bibiana Quirant-Sánchez; Herman Verheij; Sjaak Peelen; Patrick Cras; Annemiek Snoeckx; Anna Massuet-Vilamajo; Jorge Reverter; Amber Dams; Griet Nijs; Cristina Calvino-Sampedro; Ascencion López Díaz De Cerio; Susana Inoges; Felipe Prosper; Niel Hens; Heinz Wiendl; Marieke Van Ham; Zwi Berneman; Cristina Ramo-Tello

Abstract Text:

Background: Tolerogenic dendritic cell (tolDC) therapy is a promising strategy to treat autoimmune diseases since they have the potential to re-educate and modulate the pathological immune responses in an antigen-specific manner. We have developed an autologous antigen-specific cell therapy based on vitamin D3 (VitD3)-tolDC loaded with myelin peptides for treating multiple sclerosis (MS) patients.

Objectives: To demonstrate safety and feasibility of VitD3-toIDC treatment in MS patients in two phase I, open-label, dose-escalation single –center clinical trials, investigating two routes of administration: intradermal (id, MS-toIDC, NTC02618902, Belgium) and intranodal (in,TOLERVIT-MS, NTC02903537, Spain).

Methods: 18 active MS patients were included in a dose-escalation best-of-five design: Cohort 1 (5x10^6 VitD3-tolDC), Cohort 2 (10x10^6), Cohort 3 (15x10^6). Each cohort received 6 id or in (in cervical lymph nodes) administrations of myelin-loaded tolDC (first 4 every 2 weeks and last 2 every 4 weeks). Clinical, MRI and immunological monitoring were performed between 6 and 12 months after last administration.

Results: In 17 out of 18 patients enough toIDC vaccines were generated. No statistical differences between the number of adverse events (AEs) per route of administration (center) or per cohort were found. No Serious Adverse Events occurred. Remarkably, 16 out of 18 patients did not show either statistically significant disease progression or MRI activity (lesion volume) 12 months after the last toIDC administration.

Conclusions: Treatment with intradermal and intranodal myelin-specific tolDC in MS patients is safe, feasible and well-tolerated. A phase II clinical trial is currently in preparation.