Adoptive cell therapy has emerged as a promising strategy to treat cancer. It relies on patient-derived cells, such as T cells and mesenchymal stromal cells (MSCs), which are genetically engineered to become better equipped to fight cancer cells. While ex vivo genetic modification of T cells and MSCs has traditionally been performed with viral vectors, they come with concerns about safety, sustainable production and high development costs. Electroporation is a non-viral alternative transfection technology, but can lead to significant gene expression changes, phenotypic alterations, and decreased therapeutic potency. Recently, photoporation with electrospun photothermal nanofibers (PEN photoporation) was demonstrated to provide a safer alternative with minimal impact on the cell’s functionality and phenotype. The technology makes use of photothermal nanofibers which, upon stimulation with laser light, can transiently permeabilize cells to allow gene-modifying effector molecules to enter the cells. Having been thoroughly demonstrated and validated in a research setting (TRL4), this project aims to bring the PEN photoporation technology to TLR6 by developing hard- and software for automated high-throughput transfections of T cells (>1B cells/h) and MSCs (>10M cells/h). The technology will be extensively tested and validated in the cGMP compliant laboratories of the project partners for the genetic engineering of T cells and MSCs. At the same time, steps will be taken to prepare for commercialization and market deployment. By the end of the project a fully automated and validated high-throughput prototype system will be available for installation at centralized cell production facilities or ready for integration in point-of-care cell manufacturing equipment. This project aligns with the Micro-Nano-Bio challenge as it combines nanotechnology with microfluidics to enhance genetically engineered cell therapy products.

Brains for Europe Project is an initiative that comes up from the inside of the educational centres and is conceived as a solid contribution to the ongoing pedagogical renovation both thematically and methodologically. The aim of B4E is the introduction of learning in neurosciences (one of the most promising scientific areas, to which the European Commission is nowadays paying a growing attention) in educational centres, through the creation inside them of neuroscience classrooms that will open a new operative frame which we define as metaschool. Unlike top-down conventional learning, metaschool implies another type of learning, much more horizontal or even bottom-up, led by students of the different centres, in which the very students are those who decide and lead their own learning and – using the suggested tools – help to offer it to the rest of the fellow students of their own centre and to those of the other countries’ centres involved in the project. B4E has got 9 formal partners altogether: 1 foundation (and hospital), 2 companies, 5 educational centres and a mutual insurance company dedicated to education and rehabilitation in disability. Four of the partners are from Spain and the rest belongs to Turkey, Poland, Romania, France and Iceland. The countries involved are therefore 6. One has to add the involvement of 3 non-formal partners: 3 European networks such as NICE Foundation, ENVITER and HIPEN. Among the main activities of the Project, it appears in the first place a teacher training of those who will take part later in the coordination of the neuroscience classrooms (neuromentors). Once constituted a neuroscience classroom, it will be tackled in it different subjects related to the brain, to the relationship between neurosciences and technology, and to the mental disease (the question of education and rehabilitation in disability will be underlined) making the students to get opened, among other things, to the STEM Learning, to the critical thinking, to the learning to learn and to the neurological health. Students’ approach to these subjects will have an active character articulated according to the answers to concrete challenges they are going to be posed. Students will work their materials and will expose them in TED-like talks, that they will share with the rest of participants but also with the rest of the centre’s students through an e-platform. Young people taking part in the Project, among 12 and 16 years old, will get identified with it and with their role as influencers that will become an example and a motivation for the rest of their fellow students. They will be the axis around which our metaschool will spin. The idea of generating a metaschool inside a conventional educational centre, in coordination with it and profiting the channels afforded by new technologies and network communication forms provides an effective pedagogical novelty reinforced at the same time by the matter in question, decisive when it comes to inform the new pedagogical theories on the details of learning. Direct impact of B4E will be performed on 4 ambits: 1) On the directly involved students, that will take part of a different type of education, on which they have the power of decision, founded on their possibility of discovering and on their own intellectual effort, and that gets multiplied immediately through their own projection as Project-disseminators. At the same time, B4E is designed to have a great influence on students’ professional vocations, and particularly on female professional vocations. 2) On the centre’s students in general, to which it will lead to a fascinating ambit of knowledge and to which the Project will also offer a new pedagogical proposal. 3) On the centres that take part, first of all, through their teachers’ staffs, that will exercise a new and relevant pedagogical task that will contribute to offer them new possibilities and perspectives. 4) Project’s diffusion will multiply its impact at the social level, in the different countries and in the EU in general. Among its many long-term benefits, our B4E Project, including in its whole not only the urban reality but also the rural one, offers channels to take advantage of all ambits’ European youth’s talent, regardless of how limited are their opportunities in their concrete regions. That will make the difference to sound out aspects of an European collective intelligence and in the long run the Project could maybe serve as a model for future projects and make that young people can recognise themselves more easily as citizens of the same political union, the European one, reinforcing their European identity. In the end, knowing our brain is the best way of knowing ourselves and the environment we have created. Our project aims to offer the students a frame from which articulate this knowledge and set the creative bases of the very neurosciences’ evolution and of the value of its knowledge applied in the future.

Alzheimer’s disease (AD) is the leading cause of dementia and loss of autonomy in the elderly, implying a progressive cognitive decline and limitation of social activities. Progressive aging of EU population will increase the magnitude of this problem in the next decades. Currently, there is not an effective method for the early diagnosis of AD. Therefore, there is an urgent need to develop new effective early diagnostic and therapeutic strategies to help in delaying the appearance of the most adverse symptoms of this disease. To defeat this challenge, PANA project bases its approach on the importance of tau oligomers in the early pathophysiological processes of AD. The effective strategy will be based on two fundamental pillars; on one hand, efforts will be focused on multimodal PET/MRI imaging which is gaining relevance as the best solution for diagnostic purposes due to the complementary advantages of both technologies, combining the high structural characterization of tissue provided by MRI with the enhanced sensitivity of PET imaging. On the other hand, the challenging development of a theragnostic nanostructures will be focused on tau oligomers detection, which would have to deliver theragnostic agents into the brain to provide in situ diagnostic and therapeutic effects. Therefore, PANA project focuses on developing theranostic nanostructures that specifically recognize very-early molecular markers of AD, and can be detected by means of non-invasive imaging methodologies (MRI and/or PET, which are already common techniques accessible in most hospitals) and eventually provide a therapeutic action if needed. To achieve this goal, we propose a unique consortium which combines neuroscientists, nanotechnologists, molecular imaging experts, clinicians and Small/Medium/Large Enterprises in an effort to use smart nanoparticles engineered with multifunctional biomaterial to provide new very-early diagnostic tools for AD, a vital medical/social problem in EU.

In all the EU countries, rehabilitation centres specialised in the support of children with visual impairment have more and more cases of children with central visual disorders and a low vision. Our organisations have already developed methodologies and procedure for the support of children for which the visual impairment is due to a dysfunctioning of the eye, as an organ. When the visual impairement is caused by a cererbral background, the impact for children is totally different for the daily life and compensation means we use usually doesn't work. There are more and more cases and this constat is due to the improvement of medical knowledge, and that we didn't identify before the causes of their visual impairment. This is a real issue for all the rehabilitation organisations in Europe, which want to develop/set up a process of evaluation and support, as a standard for our organisations. Our experience with these children show us that they need to have a specific approach in the comprehension of the impact of their disabilities and in the support modalities to set up. And despite the improvement of scientific knowledge on this question, modalities of support are too often some individual processes, without concertation and very isolated, locally. It is important to work together on the development of a coherent and pluridisciplinary process at EU level. In consequence, the objectives of CVI Project were to gather all the experiences of the partners and to develop a common process and common tools to improve the support of visually impaired children with cerebral visual impairment. The partnership is composed of 8 organisations from Europe and one from Quebec, all are specialists in the rehabilitation of visually impaired people. Among the 9 partners, 5 of them are french speaking (MFAM, IRSAM, CRDV from France, IRSA from Belgium and INLB from Longueuil in Quebec). The 4 other organisations are coming from Spain (2), The Netherlands and Croatia. The partnership has developed : - a protocol of assessment for a pluridisciplinary assessment of central visual disorders, working with different professionals : ophtalmologists, orthoptists, neuropsychologists, working with existing tools already used, and adapted to the group when necessary. - A handbook to give the knowledge of the process, the referral to the tools used, and how it works, with the contents of the tools developed in the project.- A questionnaire for relatives and surrounding of the children to support the assessment of the children. -An individual passport in which could be described simply for the environnement the impact of disorders in the life of the child, and also with a key card, a template layed out in A5 format to know more about the context of the child concerned. - A guide (called training course) to enable the professionals to use in a suitable way the outcomes of the project for the benefit of these children. The impact of this project is very important and the number of professionals concerned by these developments is huge. with difficulty to count approximately this figure, we know that at least in the francophone network (composed of 33 organisations in francophone countries), this is approximately 5000 professionnals concerned near or far by the developments. We can say that the impact is very huge in consideration with also the other EU countries

Stem cell regenerative therapies hold great promise for patients suffering from a variety of disorders that are associated with tissue or organ injury. Regeneration relies on tissue or organ-specific stem and progenitor cells, but can also aim at promoting the endogenous repair capacity of the body. Mesenchymal stromal cells (MSC) are undergoing clinical testing in a variety of clinical conditions aiming at repair through direct or indirect mechanisms. Their ability to form bone or cartilage is used to directly repair these tissues. In other conditions their regenerative effects are based on endogenous repair through their anti-inflammatory properties. The latter mechanism is important in the treatment of acute Graft-versus-Host Disease (GvHD). We have been involved in the clinical development from the beginning and we have shown the therapeutic potential. However, no results of controlled randomized phase 3 studies have been published to date, thereby hampering safety and efficacy assessment. Within our consortium we have developed an academic infrastructure for the harmonized production of MSC. In the RETHRIM proposal this will be combined with our clinical expertise to conduct the first Europe-wide placebo controlled randomized phase III trial using MSC regenerative therapy for the treatment of steroid-resistant visceral GvHD. Central to the RETHRIM project is the clinical trial for which 150 patients will be recruited. All MSC products will be extensively analysed using molecular and functional markers, in order to develop a potency signature for the product and for the prediction of response. We also intend to collect data from additional quality of life, health technology assessment and ethical studies. We will apply for an Orphan Drug Designation in Europe and this may serve as a stepping-stone for the further commercialization of the MSC product, once a positive outcome has been obtained.