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Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk...

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Autores principales: Willekens, Barbara, Presas-Rodríguez, Silvia, Mansilla, MJ, Derdelinckx, Judith, Lee, Wai-Ping, Nijs, Griet, De Laere, Maxime, Wens, Inez, Cras, Patrick, Parizel, Paul, Van Hecke, Wim, Ribbens, Annemie, Billiet, Thibo, Adams, Geert, Couttenye, Marie-Madeleine, Navarro-Barriuso, Juan, Teniente-Serra, Aina, Quirant-Sánchez, Bibiana, Lopez-Diaz de Cerio, Ascensión, Inogés, Susana, Prosper, Felipe, Kip, Anke, Verheij, Herman, Gross, Catharina C, Wiendl, Heinz, Van Ham, Marieke (SM), Ten Brinke, Anja, Barriocanal, Ana Maria, Massuet-Vilamajó, Anna, Hens, Niel, Berneman, Zwi, Martínez-Cáceres, Eva, Cools, Nathalie, Ramo-Tello, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738722/
https://www.ncbi.nlm.nih.gov/pubmed/31501122
http://dx.doi.org/10.1136/bmjopen-2019-030309
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author Willekens, Barbara
Presas-Rodríguez, Silvia
Mansilla, MJ
Derdelinckx, Judith
Lee, Wai-Ping
Nijs, Griet
De Laere, Maxime
Wens, Inez
Cras, Patrick
Parizel, Paul
Van Hecke, Wim
Ribbens, Annemie
Billiet, Thibo
Adams, Geert
Couttenye, Marie-Madeleine
Navarro-Barriuso, Juan
Teniente-Serra, Aina
Quirant-Sánchez, Bibiana
Lopez-Diaz de Cerio, Ascensión
Inogés, Susana
Prosper, Felipe
Kip, Anke
Verheij, Herman
Gross, Catharina C
Wiendl, Heinz
Van Ham, Marieke (SM)
Ten Brinke, Anja
Barriocanal, Ana Maria
Massuet-Vilamajó, Anna
Hens, Niel
Berneman, Zwi
Martínez-Cáceres, Eva
Cools, Nathalie
Ramo-Tello, Cristina
author_facet Willekens, Barbara
Presas-Rodríguez, Silvia
Mansilla, MJ
Derdelinckx, Judith
Lee, Wai-Ping
Nijs, Griet
De Laere, Maxime
Wens, Inez
Cras, Patrick
Parizel, Paul
Van Hecke, Wim
Ribbens, Annemie
Billiet, Thibo
Adams, Geert
Couttenye, Marie-Madeleine
Navarro-Barriuso, Juan
Teniente-Serra, Aina
Quirant-Sánchez, Bibiana
Lopez-Diaz de Cerio, Ascensión
Inogés, Susana
Prosper, Felipe
Kip, Anke
Verheij, Herman
Gross, Catharina C
Wiendl, Heinz
Van Ham, Marieke (SM)
Ten Brinke, Anja
Barriocanal, Ana Maria
Massuet-Vilamajó, Anna
Hens, Niel
Berneman, Zwi
Martínez-Cáceres, Eva
Cools, Nathalie
Ramo-Tello, Cristina
author_sort Willekens, Barbara
collection PubMed
description INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. METHODS AND ANALYSIS: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. ETHICS AND DISSEMINATION: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations. TRIAL REGISTRATION NUMBERS: NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26.
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spelling pubmed-67387222019-09-25 Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration Willekens, Barbara Presas-Rodríguez, Silvia Mansilla, MJ Derdelinckx, Judith Lee, Wai-Ping Nijs, Griet De Laere, Maxime Wens, Inez Cras, Patrick Parizel, Paul Van Hecke, Wim Ribbens, Annemie Billiet, Thibo Adams, Geert Couttenye, Marie-Madeleine Navarro-Barriuso, Juan Teniente-Serra, Aina Quirant-Sánchez, Bibiana Lopez-Diaz de Cerio, Ascensión Inogés, Susana Prosper, Felipe Kip, Anke Verheij, Herman Gross, Catharina C Wiendl, Heinz Van Ham, Marieke (SM) Ten Brinke, Anja Barriocanal, Ana Maria Massuet-Vilamajó, Anna Hens, Niel Berneman, Zwi Martínez-Cáceres, Eva Cools, Nathalie Ramo-Tello, Cristina BMJ Open Neurology INTRODUCTION: Based on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach. METHODS AND ANALYSIS: Here, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo. ETHICS AND DISSEMINATION: Ethics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations. TRIAL REGISTRATION NUMBERS: NCT02618902 and NCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26. BMJ Publishing Group 2019-09-09 /pmc/articles/PMC6738722/ /pubmed/31501122 http://dx.doi.org/10.1136/bmjopen-2019-030309 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Neurology
Willekens, Barbara
Presas-Rodríguez, Silvia
Mansilla, MJ
Derdelinckx, Judith
Lee, Wai-Ping
Nijs, Griet
De Laere, Maxime
Wens, Inez
Cras, Patrick
Parizel, Paul
Van Hecke, Wim
Ribbens, Annemie
Billiet, Thibo
Adams, Geert
Couttenye, Marie-Madeleine
Navarro-Barriuso, Juan
Teniente-Serra, Aina
Quirant-Sánchez, Bibiana
Lopez-Diaz de Cerio, Ascensión
Inogés, Susana
Prosper, Felipe
Kip, Anke
Verheij, Herman
Gross, Catharina C
Wiendl, Heinz
Van Ham, Marieke (SM)
Ten Brinke, Anja
Barriocanal, Ana Maria
Massuet-Vilamajó, Anna
Hens, Niel
Berneman, Zwi
Martínez-Cáceres, Eva
Cools, Nathalie
Ramo-Tello, Cristina
Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title_full Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title_fullStr Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title_full_unstemmed Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title_short Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
title_sort tolerogenic dendritic cell-based treatment for multiple sclerosis (ms): a harmonised study protocol for two phase i clinical trials comparing intradermal and intranodal cell administration
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738722/
https://www.ncbi.nlm.nih.gov/pubmed/31501122
http://dx.doi.org/10.1136/bmjopen-2019-030309
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