Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial

Fecha de publicación: 23/04/2019

Autores de IIS La Fe

Bonaventura Casanova Estruch

Autor

Participantes ajenos a IIS La Fe

Zubizarreta, I
Florez-Grau, G
Vila, G
Cabezon, R
Espana, C
Andorra, M
Saiz, A
Llufriu, S
Sepulveda, M
Sola-Valls, N
Martinez-Lapiscina, EH
Pulido-Valdeolivas, I
Gines, MM
Tellez, N
Oreja-Guevara, C
Espanol, M
Trias, E
Cid, J
Juan, M
Lozano, M
Blanco, Y
Steinman, L
Benitez-Ribas, D
Villoslada, P

Grupos

Investigación en Neuroinmunología y Esclerosis Múltiple

Leader

Bonaventura Casanova Estruch

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 (NMOSD5). 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 lb 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.

Datos de la publicación

ISSN/ISSNe:: 0027-8424, 1091-6490
Tipo:: Article
Páginas:: 8463-8470
DOI:: 10.1073/pnas.1820039116
Factor de Impacto:: 5,165 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Métricas

Filiaciones

Keywords

immune tolerance; dendritic cells; neuromyelitis optica; multiple sclerosis; Tr1 cells

Campos de estudio

Proyectos asociados

PROYECTO CAIBER

CAI08/01/0061 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2009

RED DE BIOBANCOS (BIOBANCOS)

RD09/0076/00021 . INSTITUTO DE SALUD CARLOS III; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010

PATRONES DE RM CEREBRAL Y MEDULAR EN RELACION CON LA PRESENCIA DE AUTOANTIGENOS NEURONALES RECONOCIDOS POR INMUNOGLOBULINAS M PRESENTES EN EL LIQUIDO CEFALORRAQUIDEO DE PACIENTES DE ESCLEROSIS MULTIPLE.

Investigador Principal: ISABEL BOSCÁ BLASCO

MERCK SERONO DR. CASANOVA . ALMIRALL S.A; FUNDACIÓN BIOGEN IDEC; MERCK S.L.U; FUNDACIÓN PARA LA INVESTIGACIÓN DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA . 2010