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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 Hinajeros, 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
T cells
Dendritic cells
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.
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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
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ISSN: 0027-8424
Appears in Collections:Articles publicats en revistes (Medicina)

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