About

The Immunopathology research group is within the Immunology Service of the Germans Trias Hospital.  It is made up of an experienced interdisciplinary team that is highly motivated to carry out translational research and give support to clinical teams who are developing their own research projects to examine the mechanisms of the immune response.

In the laboratory there are advanced immunopathology diagnostics services (including: autoimmunity, allergies, immunochemistry, cellular immunology and immunodeficiency, amongst others), histocompatibility and various panels for immune monitoring of immune-mediated illnesses and immunological treatments (immune-modulating drugs, monoclonal antibodies, cellular therapies and other immunotherapeutic procedures).  Since 2008 the group has been developing new immune tolerance-inducing therapies.

The team is made up of researchers, pre-doctoral researchers and technicians who carry out prestigious research projects in the national and international arenas.  The laboratory is one of 14 centres of European excellence recognized by the Federation of Clinical Immunological Societies (FOCIS).  Since2009 it is a Consolidated Group as recognized by the Agency for Management of University and Research Grants of the Generalitat of Catalonia.  It is also the coordinator for a European network consisting of the most important groups in the field of tolergenic cellular therapies for autoimmunity, severe allergies and transplants in the field (European Action COST BM1305-AFACTT) (www.afactt.eu; www.cost.eu ).

GII3_Grup Martinez_Caceres

Group Leader

Eva Mª Martínez Cáceres(ELIMINAR), PI and Head of the Immunology Department

Research lines

Innovation and diagnostic immunology

Modern clinical immunology has to translate the new possibilities for therapies to an optimized personal treatment. This requires knowledge of the immunological status of patients in different pathological situations, selection of the best treatment and monitoring of its efficiency.  The aim of this line of research is to identify new biomarkers for diagnostics or monitoring response to treatment and to implement functional immune-phenotypic panels for patients with immune-mediated illnesses and/or in treatment with therapies that target the immune system.

Clinical epidemiology research

The objective is to better understand the immunopathology of immuno-mediated illnesses, the predictive value and pathogenicity, diagnostic and/or prognostic values of serological and genetic cellular markers available. 

Immune therapies inducing tolerance

The objective is to develop therapeutic strategies to re-establish immunological tolerance to autoantigens (in autoimmune diseases), to allergens (in severe allergies) and to alloantigen (in transplant). At the moment, the group is concentrating on autoimmune diseases of the central nervous system (multiple sclerosis).

Neuroimmunology: cellular tolerance therapy in multiple sclerosis

Codirected by Dr C. Ramo, Head of the Multiple Sclerosis Unit in the Department of Neuroscience

From in vitro studies in a mouse model of multiple sclerosis (experimental auto-immune encephalomyelitis) the group has developed a tolerogenic cell product made from autologous dendritic cells obtained from monocytes in the peripheral blood of patients.  This therapy has been developed at clinical scale complying with the conditions of Good Manufacturing Practice (GMP) and pending approval by the AEMPS with the aim of carrying out a Phase i/IIa clinical trial soon.

Active projects

Immunoterapia con células dendríticas tolerogénicas en esclerosis múltiple. Estudios preclínicos e immunomonitorización

Code: FIS21000
Principal Investigator: Eva Martínez Cáceres
Start date:2015
End date:2018

Inducción de TOLERancia con células dendríticas tratadas con VITamina D3 y cargadas con péptidos de mielina, en pacientes con eSclerosis Múltiple: TolerVit-MS

Code: PI16/01737
Principal Investigator: Cristina Ramo
Start date:01/01/2017
End date:30/06/2021

RESUMEN (Objetivos y Metodología del Proyecto): La esclerosis múltiple ltM) es una enfermedad autoinmunitaria crónica neurodegenerativa del Sistema nervioso central (SNC). Afecta mayoritariamente a adultos jóvenes y no tiene cura. Las terapias actuales deprimen inespecíficamente el sistema inmunitario, pueden dar lugar a afectos adversos severos y no han demostrado de forma convincente evitar ni retrasar la discapacidad largo plazo. Por lo tanto, el desarrollo nuevas estrategias terapéuticas sigue siendo de una gran relevancia. El avance en el conocimiento sobre los mecanismos de tolerancia inmunitaria llevado al desarrollo de terapias celulares especificas inductoras de tolerancia (TCT) que tienen el objetivo de evitar reacciones autoinmunitarias y modificar el curso de enfermedades autoinmunes a largo plazo.  Así, las TCT se perciben como una estratégia terapéutica eficaz, no sólo de forma general sino específica de cada paciente, porque pueden personalizarse. Las TCT pueden establecer un punto de inflexión en el tratamiento de los pacientes con EM. Objetivo principal: Demostrar la seguridad y tolerabilidad de una terapia celular basada en células dendríticas tolerogénicas autólogas tratadas con Vitamina 03 (tolDC-VitD3) y cargadas con un grupo de péptidos de la mielina para restablecer la tolerancia inmunitaria en pacientes con EM. Metodología: Realización de un ensayo clínico Fase I multicéntrico, abierto, de escalado de dosis (5-10-15 millones células x 6 administraciones), por vía intraganglionar, en 12 pacientes con EM que cumplan los criterios inclusión y ninguno de exclusión. Monitorización clínica, radiológica (RM cerebral) e inmunológica (definición de paneles de biomarcadores inmunitarios en sangre periférica e inmunomonitorización de los pacientes tratados).

Neuronal self-renewal by antigen-specific tolerization in multiple sclerosis reinstalling the balance between inflammation and regeneration

Code: EUR44500

Principal Investigator: Eva Martínez Cáceres
Start date:2018
End date:2022

 Inducción de Tolerancia: Nuevas vías y dianas terapéuticas

Code: FIS36400
Principal Investigator: Eva Martínez Cáceres
Start date:2018
End date:2020

A negative dendritic-cell based vaccine for the treatment of multiple sclerosis: a first-in-man multicenter trial

Code: IWT17400
Principal Investigator: Eva Martínez Cáceres
Start date:2015
End date:2019

Neuronal Self-Renewal By Antigen-Specific Tolerization In Multiple Sclerosis Reinstalling The Balance Between Inflammation And Regeneration (RESTORE)

Code: 779316
Principal Investigator: Eva Martínez Cáceres, Cristina Ramo Tello
Start date:01/01/2018
End date:31/12/2022

Scientific publications

Zurera C, Hernandez A, Teniente A, Fuster D, Martinez EM, Muga R, Zuluaga YP. Phenotypes of NK cells and the activation profile of T cells in the early stages of alcohol liver diseases. Journal of Hepatology. 2022 Jul. 77. DOI: 10.1016/S0168-8278(22)00772-3

Morante-Palacios O, Godoy-Tena G, Calafell-Segura J, Ciudad L, Martínez-Cáceres EM, Sardina JL, Ballestar E. Vitamin C enhances NF-κB-driven epigenomic reprogramming and boosts the immunogenic properties of dendritic cells. Nucleic Acids Res. 2022 Oct. 28;50(19). DOI: 10.1093/nar/gkac941

Català-Moll F, Ferreté-Bonastre AG, Godoy-Tena G, Morante-Palacios O, Ciudad L, Barberà L, Fondelli F, Martínez-Cáceres EM, Rodríguez-Ubreva J, Li T, Ballestar E. Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis. Cell Rep. 2022 Jan. 18;38(3). DOI: 10.1016/j.celrep.2021.110244

Additional information

The Group is a member of the INSTRUCT Consortium

A network of European scientists from academic and industry focused on developing innovative myeloid regulatory cell (MRC)-based immunotherapies. The consortium recevies funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860003.

News

- Recerca, Innovació, Projectes

Dos projectes de l'IGTP, finançats amb 1,6 milions d'euros per la Comissió Europea

La Comissió Europea ha concedit dos projectes a l'IGTP dins del Programa HORIZON, que sumen un total d'1.670.346 euros de finançament i tracten sobre el desenvolupament preclínic d'immunoteràpies.

- Recerca

Noves dades sobre els mecanismes de les teràpies tolerogèniques per reduir la immunitat agressiva en tractaments per a malalties autoimmunes i inflamatòries

El grup de recerca d'Immunopatologia, amb el Servei d'Immunologia i la Unitat d'Esclerosi Múltiple a l'Hospital Germans Trias continuen les línies de recerca per a nous tractaments contra l'esclerosi múltiple. El seu darrer article, publicat a Frontiers of Immunology, examina els mecanismes pels quals les cèl·lules dendrítiques de la vitamina D3 s'utilitzen per alterar els limfòcits propis dels pacients per inhibir respostes autoimmunes.

+ Notícies

Contact

Eva Mª Martínez Cáceres, Head of Immunology Department, Germans Trias i Pujol University Hospital

(+34) 93 497 8666 / (+34) 93 497 8656

emmartinez.germanstrias(ELIMINAR)@gencat.cat