Eight hundred and fifty million people worldwide are currently affected by chronic kidney disease (CKD), which is also the 11th leading cause of mortality worldwide. CKD can occur from a multitude of causes including diabetes and high-blood pressure. Moreover, recent clinical and experimental studies have shown that CKD is closely interconnected with acute kidney injury (AKI) as well. Currently available in vitro models show limited relevance to study AKI, especially drug- and virus- induced AKI, due to the poor functionality and relevance compared to a diseased human tissue. BIRDIE aims at developing three-dimensional (3D) in vitro human renal tubulointerstitium (TI) models to enable viral infection and nephrotoxicity studies while creating a robust platform to address other diseases and treatment innovations in the future. Two enabling technologies, bioprinting and organ-on-chip, will be combined to build a microphysiological relevant TI model. Primary human cells and induced pluripotent stem cells will be used to generate kidney models, and combined with the aforementioned techniques model envisioning a reliable screening platform for future patient specific therapies. Our ambition is to create a new 3D renal in vitro model allowing an unprecedented degree of mimicry and function compared to a human kidney. While developing the model focusing on the applications mentioned before, our goal is to make it broadly applicable to the multitude of kidney-related diseases.

In the aging society, disease burden, such as degenerative diseases and cancer are rising while drug development successes are limited, due to high drug failure rates in the transition from animal experimentation to human patients. This demands re-thinking of the currently used models. Advances in stem cell biology and microfluidics have created new human organ models. These models are neither fully understood, nor fully mimicking the complexity of the tissue. With this new ability to build human stem cell-based models, we have a responsibility to drive these models to implementation – aiming to replace animal experimentation and provide next generation patient avatars for precision medicine. TOP-GUT combines cutting-edge basic and translational science with an outstanding program of education to unleash the full potential of new human organ models, specifically patient-derived organoids and organ-on-chip devices. TOP-GUT will focus on the gastrointestinal (GI) tract, which is the bodies second largest interface with the environment. It is medically highly relevant not only as a major site of cancer development, as target of infectious agents, and as site of inflammatory diseases, but also as one of the major organs for drug uptake and relevance in toxicology. TOP-GUT aims to significantly contribute to our understanding of the current GI models, establish new tools and protocols for more complex GI models, and advance the use of GI models for personalised medicine. In addition, TOP-GUT will address ethical and legal issues to foster acceptance and implementation of the GI models. TOP-GUT will build a solid European network to cooperate, standardize and push GI models into applications, bringing together academia and industry. Together, TOP-GUT educates the next generation of researchers to become new leaders in the field and to drive the implementation of new stem cell based human models to replace animal experimentation in academia and industry.

There is an increasing prevalence of chronic diseases caused by undesired immune reactions (>10%) with high burden for the both patients (chronicity, organ failure, early death, decreased QoL) and society (EU:>100 bn €/a direct health costs) as current therapies are limited in efficacy and do not reshape sustainably the disturbed immune balance. Our ultimative goal is to develop a safe and efficient cell therapy based on genome-edited T cells with redirected specificity to sustainably combat IgA nephropathy (IgAN) - the most common glomerulonephritis and one of the most common causes of end-stage renal disease with unmet medical need. Our specific cell therapy approach is also suitable for other diseases with selective B-cell pathogenesis, such as IgA myeloma, IgA related celiac disease and rheumatoid arthritis, but as a blueprint also for diseases of other Ig classes (e.g. IgG4). Our novel concept offers a specific form of immunosuppression via Ig-(sub)class targeting & glycosylation targeting with redirected T cells in autoimmune diseases. Methodically, we benchmark three promising genome editing technologies, develop new standards for safety assessment and preclinical performance evaluation. At the end we will have a lead candidate of a new "living drug" product envisioned as a one-time treatment for IgAN and other IgA-associated that will be ready to enter clinical FIH trials (entry into TRL6). In addition, geneTIGA delivers enabling technology toolboxes with exploitation options beyond of the core project. They might de-risk and accelerate the development of next-generation gene and cell products in general. The project has thus, besides its scientific value, a high impact not only on the affected patients with IgAN and related immune diseases, but also for the European society by reducing the health economic burden caused by progressive chronic kidney disease, as well as by triggering innovation and business options in Europe's biotech and pharma field.

Recently, a new class of “living drugs” has been developed – Advanced Therapies which aim to transform the current focus of “treatment of disease” into one that concentrates on “restoration of health” with promising results in a broad field of Regenerative Medicine, including targeted immune reconstitution for cancer treatment. Advanced Therapies are game changing in Health Care and have a rapidly expanding market size of approximately 12 and 50 bn € expected by 2020 and 2030, respectively. There is great value in European science and technology on Advanced Therapies but Europe has been losing ground because of scattered and underpowered efforts. If Europe wants a leading role in this emerging field in the future, a mission-driven approach is required to make the transforming promise of Advanced Therapies a reality. The development of new Advanced Therapy products and their implementation in clinical practice will enhance the value-based outcome of patients. Measurable by having dozens of premier-league Advanced Therapy Products “discovered & made in Europa” by 2030 and beyond. Bringing affordable, standard-of-care for currently incurable diseases which are accessible for every European citizen who need it to RESTORE Health. We propose a mission-driven programme led by the candidate LSRI RESTORE, aiming to build a coordinated, financially strong European partnership between different areas of interest and cross-sectors involving academia, industry, regulatory authorities, health care, patient organisations, and public society. In order to guarantee a smart start of the LSRI from 2021 onwards, the preparation phase aims to involve the growing RESTORE community even more closely in working groups on identified tasks and to jointly complete the RESTORE agenda for Research & Innovation Actions as well as Coordination & Support Actions. The deliverables of RESTORE will allow Europe to gain a world leading health position within this emerging field.

Adoptive transfer of regulatory T cells (Treg) is a promising new therapeutic option to reshape undesired intra-tissue immune imbalance in immune-related disease entities. It supports long-term function of allografts and use of Advanced Therapy Medicinal Products (ATMP) by overcoming the challenge of unwanted immune reaction by the recipient of the ATMP. Therefore, adoptive Treg therapy is a potential game changer in health care, particularly in immune diseases, organ & hematopoietic stem cell (HSC) transplantation, and regenerative medicine, including gene therapy. Based on the Triple-T concept - Transdisciplinarity, Technology, Translation - the major goal of RESHAPE is to transform the treatment of patients suffering from undesired immunity/inflammation, who presently have limited curative treatment options, by applying novel Treg approaches that overcome the limitations of 1st generation Treg product developments. Members of the consortium, with academic & biotech backgrounds, are pioneers in the development of Treg therapy from basic science to very recent encouraging First-In-Human (FIH) clinical trials of the 1st generation Treg products. They have a longtrack record of collaboration, including in EC-funded projects. The first clinical trials were performed to combat organ transplant rejection and Graft-versus-Host-Disease. However, promising preclinical studies offer a broad application field of Treg therapy beyond allotransplantation. Based on our preclinical & clinical data, we have identified several opportunities for improving Treg therapy, such as enhanced antigen specificity & functional stability, and recipient conditioning, that will be addressed by RESHAPE. The next-generation Treg products, developed by advanced technologies including CRISPR/Cas9, will be tested on platforms applying new methods for cell characteristics in both in vivo /in vitro models, and finally proven in FIH-clinical trials accompanied by biomarker and health economic studies