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Title: | Immune Tolerance in Multiple Sclerosis and Neuromyelitis Optica with Peptide-Loaded Tolerogenic Dendritic Cells in a Phase 1b Trial |
Author: | Zubizarreta, Irati Flórez Grau, Georgina Villa, Gemma Cabezón Cabello, Raquel España, Carolina Andorra, Magi Saiz Hinarejos, Albert Llufriu Duran, Sara Sepúlveda, María Sola Valls, Nuria Hernández Martinez Lapiscina, Elena Pulido Valdeolivas, Irene Casanova, Bonaventura Martinez-Gines, Marisa Tellez, Nieves Oreja-Guevara, Celia Español, Marta Trias, Esteve Cid Vidal, Joan Juan, Manel Lozano Molero, Miguel Blanco, Yolanda Steinman, Lawrence Benitez Ribas, Daniel Villoslada, Pablo |
Keywords: | Cèl·lules T Cèl·lules dendrítiques Antígens T cells Dendritic cells Antigens |
Issue Date: | 23-Apr-2019 |
Publisher: | National Academy of Sciences |
Abstract: | There are adaptive T-cell and antibody autoimmune responses to myelin-derived peptides in multiple sclerosis (MS) and to aquaporin-4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSDs). Strategies aimed at antigen-specific tolerance to these autoantigens are thus indicated for these diseases. One approach involves induction of tolerance with engineered dendritic cells (tolDCs) loaded with specific antigens. We conducted an in-human phase 1b clinical trial testing increasing concentrations of autologous tolDCs loaded with peptides from various myelin proteins and from AQP4. We tested this approach in 12 patients, 8 with MS and 4 with NMOSD. The primary end point was the safety and tolerability, while secondary end points were clinical outcomes (relapses and disability), imaging (MRI and optical coherence tomography), and immunological responses. Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable clinically in terms of relapse, disability, and in various measurements using imaging. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of a regulatory T cell, known as Tr1, by week 12 of follow-up. In this phase 1b trial, we concluded that the i.v. administration of peptide-loaded dendritic cells is safe and feasible. Elicitation of specific IL-10 production by peptide-specific T cells in MS and NMOSD patients indicates that a key element in antigen specific tolerance is activated with this approach. The results warrant further clinical testing in larger trials. |
Note: | Reproducció del document publicat a: https://doi.org/10.1073/pnas.1820039116 |
It is part of: | Proceedings of the National Academy of Sciences of the United States of America - PNAS, 2019, vol. 116, num. 17, p. 8463-8470 |
URI: | http://hdl.handle.net/2445/172429 |
Related resource: | https://doi.org/10.1073/pnas.1820039116 |
ISSN: | 0027-8424 |
Appears in Collections: | Articles publicats en revistes (Medicina) |
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