ReSToRe will test a new therapeutic approach based on patients’ own cells. This cell therapy, a type of personalised medicine, is currently being lined up for an initial Phase 1 study in patients with MS. The researchers have developed what are known as ‘tolerance-inducing’ or tolerogenic dendritic cells (tolDC) – a special category of immune cells that function as the immune system’s master switch.

In MS, the immune system has derailed, setting a cascade of processes in motion that ultimately results in damage to the body’s own cells and molecules.

After being treated with vitamin D in a laboratory, tolDC are re-administered to the patient and are then able to re-educate the patient’s immune system, interfering directly with the underlying disease processes.

Investigating the safety and feasibility of the vaccine will be a crucial step in the development of novel treatment strategies for MS. In order to perform this clinical trial, the researchers received support from the European Union’s Horizon 2020 research and innovation programme, enabling collaboration among several EU research institutes and companies.

Our Mission

H2020 ReStoRe’s goal

This project is based on the major progress that has been made in the understanding and treatment of MS and focuses on the development of more selective immunomodulatory therapies with fewer side effects and with the potential for long-term disease remission. The overall goal of the ReSToRe project is to assess the safety and demonstrate first proof-of-concept of administering clinical-grade vitamin D₃-treated tolDC loaded with myelin-derived peptides via different administration routes to treat a well-defined subpopulation of MS patients.

What is MS? Context of the problem

In young adults, multiple sclerosis (MS) is the main cause of non-traumatic neurological disability with no cure available to date. Around 500,000 people in Europe and 2.5 million people worldwide suffer from MS.

Dendritic cells

DC are a highly specialized population of white blood cells that are capable of orchestrating the immune responses. In their immature state, DC reside in the peripheral tissues, such as the skin, airways and intestine, where they function as the “sentinels” of the immune system, i.e. they patrol the body to capture antigens, including self-antigens, invading pathogens and certain malignant cells.

Who is who

University of Antwerp, Belgium

Antwerp University Hospital, Belgium

Universidad Navarra (UNAV), Spain

Icometrix, Leuven, Belgium

Lygature, the Netherlands

Catalan Institute of Health (ICS)

Sanquin

Wilhelms University Münster, Germany

News & Events

19th February 2023

We Present at the 2023 Annual Meeting of the CMSC

CMSC is the organization of healthcare professionals committed to providing optimal service to everyone affected by MS. They meet each year to discuss the progress of MS research and care. We are pleased that the organizers of the 2023 Annual Meeting, to be held in June in Aurora, Colorado, have given us the opportunity to present ReStoRe’s research. Our researcher, Barbara Willekens, PhD, will give a presentation entitled ‘Intradermal and Intranodal Administration of Vitamin D3-Induced Tolerogenic Dendritic Cells Is Safe and Feasible in Two Phase I Clinical Trials’ on June 2, 2023 at 3:05 PM.

27th January 2023

5th annual consortium meeting

On Friday 27/1, the consortium convened in Antwerp, after more than 2 years of virtual meetings. At this meeting, we welcomed our external scientific experts, members of the Data Safety Monitoring Board and the Stakeholder Committee and provided them with an overview of the Phase I clinical trial, which we have successfully completed. In addition, we looked ahead to the coming years, in particular the start of the Phase II trial. Again, it was a very interesting meeting.

23rd December 2022

Update on the Phase II Clinical Trial

The phase II clinical trial application is successfully submitted at the ethical committee and national competent authorities. We expect their feedback within the next 90 days.

1st December 2022

The Fifth Consortium Meeting is postponed

The 5th annual consortium meeting, which was planned in December 2022, is postponed to early 2023. During this meeting we will provide our stakeholders with a complete overview of the acquired data from phase 1.

For older news items

Publications

Combined Therapy of Vitamin D3-Tolerogenic Dendritic Cells and Interferon-β in a Preclinical Model of Multiple Sclerosis.
Author(s): Quirant-Sánchez B, Mansilla MJ, Navarro-Barriuso J, Presas-Rodríguez S, Teniente-Serra A, Fondelli F, Ramo-Tello C, Martínez-Cáceres E.
Published in: Biomedicines. 2021 Nov 24;9(12):1758.

Safety and immunological proof-of-concept following treatment with tolerance-inducing cell products in patients with autoimmune diseases or receiving organ transplantation: A systematic review and meta-analysis of clinical trials.
Author(s): Willekens B, Wens I, Wouters K, Cras P, Cools N.
Published in: Autoimmun Rev. 2021 Aug;20(8):102873

Made to Measure: Patient-Tailored Treatment of Multiple Sclerosis Using Cell-Based Therapies.
Author(s): Wens I, Janssens I, Derdelinckx J, Meena M, Willekens B, Cools N.
Published in: Int J Mol Sci. 2021 Jul 14;22(14):7536.

Transfection of Vitamin D3-Induced Tolerogenic Dendritic Cells for the Silencing of Potential Tolerogenic Genes. Identification of CSF1R-CSF1 Signaling as a Glycolytic Regulator.
Author(s): Mansilla MJ, González-Larreategui I, Figa-Martín N, Barallat J, Fondelli F, Sellés-Rius A, Quirant-Sánchez B, Teniente-Serra A, Martínez-Cáceres E.
Published in: Int J Mol Sci. 2021 Jul 8;22(14):7363.

Vitamin D3-Induced Tolerogenic Dendritic Cells Modulate the Transcriptomic Profile of T CD4+ Cells Towards a Functional Hyporesponsiveness.
Author(s): Navarro-Barriuso J, Mansilla MJ, Quirant-Sánchez B, Teniente-Serra A, Ramo-Tello C, Martínez-Cáceres EM.
Published in: Front Immunol. 2021 Jan 20;11:599623.

Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy
Author(s): M. J. Mansilla, S. Presas-Rodríguez, A. Teniente-Serra, I. González-Larreategui, B. Quirant-Sánchez, F. Fondelli, N. Djedovic, D. Iwaszkiewicz-Grześ, K. Chwojnicki, Đ. Miljković, P. Trzonkowski, C. Ramo-Tello, E. M. Martínez-Cáceres
Published in: Cellular & Molecular Immunology, Issue 18/6, 2021, Page(s) 1353-1374, ISSN 1672-7681

Guidelines for analysis of low-frequency antigen-specific T cell results: Dye-based proliferation assay vs 3H-thymidine incorporation
Author(s): Daniela Di Blasi, Iris Claessen, Annelies W. Turksma, Josine van Beek, Anja ten Brinke
Published in: Journal of Immunological Methods, Issue 487, 2020, Page(s) 112907, ISSN 0022-1759

Ways Forward for Tolerance-Inducing Cellular Therapies- an AFACTT Perspective
Author(s): Anja ten Brinke, Marc Martinez-Llordella, Nathalie Cools, Catharien M. U. Hilkens, S. Marieke van Ham, Birgit Sawitzki, Edward K. Geissler, Giovanna Lombardi, Piotr Trzonkowski, Eva Martinez-Caceres
Published in: Frontiers in Immunology, Issue 10, 2019, ISSN 1664-3224

Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonized study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration
Author(s): Willekens B, Presas-Rodríguez, Mansilla M, Derdelinckx J, Lee W-P, Nijs G, De Laere M, Wens I, Cras P, Parizel PM, Van Hecke W, Ribbens A, Billiet T, Adams G, Couttenye M, Navarro-Barriuso J, Teniente-Serra A, Quirant-Sánchez B, López-Díaz de Cerio A, Inogés S, Prósper F, Kip A, Verheij H, Gross CC, Wiendl H, van Ham SM, ten Brinke A, Barriocanal AM, Massuet-Vilamajó A, Hens N, Berneman Z,
Published in: BMJ Open, Issue accepted for publication 23/7/2019, 2019, ISSN 2044-6055

MAP7 and MUCL1 Are Biomarkers of Vitamin D3-Induced Tolerogenic Dendritic Cells in Multiple Sclerosis Patients
Author(s): Juan Navarro-Barriuso, María José Mansilla, Bibiana Quirant-Sánchez, Alicia Ardiaca-Martínez, Aina Teniente-Serra, Silvia Presas-Rodríguez, Anja ten Brinke, Cristina Ramo-Tello, Eva M. Martínez-Cáceres
Published in: Frontiers in Immunology, Issue 10, 2019, ISSN 1664-3224

Beyond the Magic Bullet: Current Progress of Therapeutic Vaccination in Multiple Sclerosis
Author(s): Barbara Willekens, Nathalie Cools
Published in: CNS Drugs, Issue 32/5, 2018, Page(s) 401-410, ISSN 1172-7047

Contact us

Patient information

This is a medical-scientific study, more specifically an open-label Phase I clinical trial, limited to Belgium and Spain in which about twenty patients per country will participate. Below you will find non-committal information about the study. Feel free to share and discuss this information with your neurologist.

Patiënt informatie

Dit is een medisch-wetenschappelijk onderzoek, meer bepaald een open-label fase I klinische studie, beperkt tot België en Spanje waaraan in totaal een twintigtal patiënten zullen deelnemen. Hieronder vindt u, geheel vrijblijvend, meer informatie over de studie. Indien u dat wenst, kan u deze informatie ook delen en bespreken met uw neuroloog.

Verder lezen...

Información del paciente

El estudio RESTORE está diseñado para personas que sufren esclerosis múltiple (EM). Se trata de un ensayo clínico Fase I que se realiza en 2 países: Bélgica y España. Está previsto que en cada uno de los países participen unos veinte pacientes. A continuación encontrará información sobre este ensayo.

Informationen zum Patienten

Dies ist eine medizinisch-wissenschaftliche Studie, genauer gesagt eine offene klinische Phase-I-Studie, beschränkt auf Belgien und Spanien, an der insgesamt zwanzig Patienten teilnehmen werden. Nachfolgend finden Sie unverbindlich weitere Informationen zur Studie. Wenn Sie möchten, können Sie diese Informationen auch mit Ihrem Neurologen teilen und besprechen.

Information du patient

Une traduction sera disponible bientôt.