TOLERATE training network aims at training Doctoral Candidates’ (DCs) to acquire the skills to develop different innovative strategies to treat autoimmune diseases, to identify the most promising strategies or a combination of strategies, to setup clinical trials and to develop a roadmap to bring a novel therapeutic agent to the market. This all will be done in a highly interdisciplinary and intersectoral environment. Interdisciplinarity allows to introduce innovative tolerogenic therapies developed for cancer, Chimer Antigen Receptor (CAR)-T cell therapies, into the world of autoimmune disease and to apply nanotechnology and protein-engineered tolerogenic vaccines to re-establish immune tolerance in autoimmune disease. Both the presence of academia and industry provides a platform for in-depth preclinical studies and a realistic possibility for future commercialization of the novel therapies. Clinicians in the consortium with expertise in setting-up and running clinical trials for novel drugs assure that developed novel therapies in TOLERATE will find their way to the clinic in the future. Developing novel therapies for autoimmune diseases goes close together with a thorough knowledge on the long-term consequences of living with an autoimmune disease. Since many autoimmune diseases are rare diseases, setting up international uniform databases and biobanks is crucial to understand the long-term pathophysiology of the disease and to guarantee optimal use of (novel) therapies. TOLERATE will train 8 DCs who will hence have the expertise and skills to work in and setup interdisciplinary and intersectoral projects. The ground-breaking training programme will provide the DCs with a unique clinical training. Additional training in ethical, regulatory and legal aspects together with a training in innovation management of therapeutics and diagnostics for autoimmune diseases will prepare the DCs for the European job market.

Participating in TOLERATE offers Doctoral Candidates many unique opportunities, including:

• A project as Marie Skłodowska Curie trainee in one of the participating institutions with the intention of receiving a doctoral degree (PhD).
• State-of-the art, exciting research in an international consortium with highly integrated research projects.
• Expert training in immunology, autoimmune disease, and drug development and transferable skills including communication skills (verbal and written), management and entrepreneurial and career development skills.
• At least six months of research training in the lab of other consortium member, mostly in a different EU country, and all including a 6-week clinical training.
• Training in both academic and non-academic research environments.
• Salary according to EU guidelines for Marie Skłodowska Curie trainees, including mobility payments and family allowances where applicable.

Eligible candidates must:

• hold a Master’s degree or equivalent in a field of science relevant to their chosen project (see below)
• demonstrate a history of academic excellence
• demonstrate an affinity for one or more of the following disciplines: biomedical sciences, cell biology, biochemistry, nanotechnology, cell therapy, drug development, clinical trials speak and write fluently in English
• be fascinated by scientific research and innovation
• be motivated, enthusiastic and eager to learn
• be able to work methodically and accurately
• be able to work independently yet also being a team player
• have a creative mind and strong problem-solving skills
• have a good writing and oral expression
• be willing to do secondments in different EU countries
• not hold a doctoral (PhD) title
• not have resided in the country where the recruiting institution is located for more than 12 months in the 3 years before recruitment
• be available to start their project no later than April 2023

INDIVIDUAL PROJECT DESCRIPTION (find full information on PDF)

DC1: Long-term consequences of living with TTP: design novel treatment regimens for iTTP to reduce comorbidities.

Hosting Institution Assistance Publique Hopitaux De Paris (France)

Supervisor Paul Coppo, Agnès Veyradier

Email address for the applicationspaul.coppo@aphp.fr; agnes.veyradier@aphp.fr

Subject area Immune-mediated TTP, ADAMTS13, cardiovascular risk factors, comorbidities, relapse, refractoriness, life expectancy, registry cross-sectional analysis, biobank collection and analysis, clinical trials.

Project-specific selection criteria DC1 will exhaustively analyze the French registry for TMA (French reference center for TMA) to review a 25-year experience of TTP treatment and patients’ follow-up. DC1 will specifically analyze comorbidities and cardiovascular risk factors in TTP patients. Based on this retrospective analysis and comparison with the international literature, recommendations/guidelines will be designed.

DC2: UniCAR-T cell therapy to treat autoimmune disease: iTTP as the model system

Hosting Institution Katholieke Universiteit Leuven (Belgium)

Supervisor Karen Vanhoorelbeke

Email address for the applicationskaren.vanhoorelbeke@kuleuven.be

Subject area Genetic engineering, UniCAR-T cell therapy, mouse models, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura.

Project-specific selection criteria DC2 will develop the innovative UniCAR-T cell therapy to treat the autoimmune disease using immune-mediated thrombotic thrombocytopenic purpura (iTTP) as a model disease. UniCAR-T cells will be generated via genetic engineering. The UniCAR-T cell therapy will be tested both in vitro and in vivo in a mouse model of iTTP. Master degree with distinction required.

DC3: RevCAR-T cell therapy to treat autoimmune disease: iTTP as the model system

Hosting Institution Helmholtz-Zentrum Dresden-rossendorf Rossendorf e.V. (Germany)

Supervisor Michael Bachmann

Email address for the applications Interested candidates are invited to apply for this position via the HZDR career website

Subject area Genetic engineering, RevCAR-Tcell therapy, mouse models, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura

Project-specific selection criteria DC3 will develop the innovative RevCAR-T cell therapy to treat the autoimmune disease using immune-mediated thrombotic thrombocytopenic purpura (iTTP) as a model disease. RevCAR-T cells will be generated via genetic engineering. The RevCAR-T cell therapy will be tested both in vitro and in vivo in a mouse model of iTTP.

DC4: TCR-engineered Tregs to treat autoimmune disease: iTTP as the model system

Hosting Institution ANICELLS (Belgium)

Supervisor Nathalie Cools

Email address for the applicationsnathalie@anicells.com

Subject area Genetic engineering, Treg cell therapy, mouse models, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura

Project-specific selection criteria DC4 will develop the innovative TCR-engineered Tregs to treat the autoimmune disease using immune-mediated thrombotic thrombocytopenic purpura (iTTP) as a model disease. TCR-engineered Tregs will be generated via genetic engineering. The TCR-engineered Tregs cell therapy will be tested both in vitro and in vivo in a mouse model of iTTP. Master’s degree with distinction required in Bio(medical) Engineering, Biotechnology, Biochemistry, Pharmacy or equivalent qualifications. Practical laboratory experience preferred.

DC5: Engineered protein based tolerogenic vaccines: iTTP as the model system

Hosting Institution Stichting Sanquin Bloedvoorziening (The Netherlands)

Supervisor Jan Voorberg

Email address for the applicationsj.voorberg@sanquin.nl

Subject area Tolerogenic liver targeting vaccines, red blood cell based tolerogenic approaches, CRISPR-Cas9 based genome-editing, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura.

Project-specific selection criteria DC5 will develop novel tolerogenic approaches to treat autoimmune disease using immune-mediated thrombotic thrombocytopenic purpura (iTTP) as a model disease. Liver directed tolerogenic vaccines targeting surface receptors on liver sinusoidal endothelial cells (LSEC) will be employed as well as genome-engineered red blood cell based tolerogenic vaccines will be generated. The novel tolerogenic therapies will be tested in vitro and in vivo in a mouse model of iTTP. Master degree with distinction required.

DC6: Nanoparticle-mediated approaches to restore tolerance in iTTP

Hosting Institution AHEAD THERAPEUTICS SL (Spain)

Supervisor Marta Vives-Pi

Email address for the applicationsmvives@igtp.cat

Subject area Liposomes, antigen specific tolerance induction, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura.

Project-specific selection criteria DC6 will develop innovative TTP PS-liposomes to treat the autoimmune disease using immune-mediated thrombotic thrombocytopenic purpura (iTTP) as a model disease. Liposomes will be generated and tested both in vitro and in vivo in iTTPs patients’ lymphocytes and in a mouse model of iTTP respectively.

DC7: ADAMTS13 (targeted) clearance

Hosting Institution Royal College of Surgeons in Ireland (Ireland)

Supervisor James O’Donnell

Email address for the applicationsjamesodonnell@rcsi.ie

Subject area Molecular medicine and cellular biology, including genetic engineering and protein biochemistry.

Project-specific selection criteria DC7 will make new discoveries in defining the biology through which ADAMTS13 is cleared from the blood and characterize the cellular pathways responsible. Findings will be used to develop novel targeted ADAMTS13 therapies for patients with thrombotic thrombocytopenic purpura (TTP). Master degree with distinction required.

DC8: Understanding the immune response during long term follow-up

Hosting Institution Semmelweis Egyetem (Hungary)

Supervisor Zoltán Prohászka

Email address for the applicationsProhaszka.zoltan@med.semmelweis-univ.hu

Subject area Immunoassay development, ADAMTS13, cytokine and complement determinations, autoimmune disease immune-mediated thrombotic thrombocytopenic purpura

Project-specific selection criteria DC8 will develop an assay to measure opening antibodies in the iTTP patient's samples. A complex clinical study with measurement of cytokine profiles, complement profiles, ADAMTS13 antigen, ADAMTS13 autoantibody (total and inhibitory) levels will also be executed in iTTP to understand the complex immune pathophysiology in this disease. DC8 should have expertise in immunoassays, FACS analysis, multiplex assays, protein analysis techniques, molecular biology, clinical and laboratory immunology training, medical training.