CHU

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

“HAP2” aims to develop stratified host-directed drugs and biomarkers to enhance the prevention and the treatment of hospital-acquired pneumonia (HAP) and develop precision medicine in infectious diseases. HAP is an infectious disease of major concern in the world, and the most frequent cause of hospital-acquired infections with 500,000 episodes being treated every year in Europe. Despite the development of European recommendations, the incidence remains high, with dramatic medical consequences: existing therapies and preventive measures do not result in the expected favourable outcome (clinical cure and survival) for 30% of patients. HAP are moreover the main cause of antibiotic consumption in European hospitals and are increasingly induced by drug-resistant pathogens. New, alternative and more effective host-targeted strategies are therefore urgently needed to fight antibiotic resistance. The ambition of “HAP2” is to revolutionize the management of HAP: capitalising on the novel concept of critical-illness related immunosuppression altering the host-pathogens interactions, we propose a complete reappraisal of the physiopathology of HAP based on the concept of respiratory dysbiosis. “The HAP2” project will reach two ground-breaking objectives in the field of bacterial infections: first the development of host-targeted approaches for the prevention and the treatment of a severe bacterial infection through the supplementation of the IL-12/IFN-γ axis which is defective in patients at risk of pneumonia; second the development of a clinico-biological score based on an integrative assessment of the host-pathogen interactions and genetic variation, to predict the course of HAP and the response to treatment. Our interdisciplinary consortium, bringing together 10 partners from academia and industry with expertise in clinical trials, immunology, microbiome analysis, omics and social sciences is uniquely placed to achieve this ambition within this 5-year project.