Glioblastoma (GBM) is the most lethal brain malignancy in adults and is associated with a poor prognosis. Therapy options in GBM patients are largely limited by the highly immunosuppressive tumor microenvironment (TME). Identifying and disrupting these immunosuppressive communication circuits between immune cells and the tumor is key to reinvigorate the immune system’s ability to fight the tumor. Here, we combine my previous experience in the analysis of single cell data at the neuro-immune interface with Prof. Zeiser’s patient-centered expertise in developing novel therapy options to combat tumor immune escape. In this highly complementary setting, we propose a data-driven approach to trace and perturb inhibitory communication circuits elicited by the TME across space and time with the aim to discover novel immunotherapeutic targets in GBM. Using a novel temporal single cell technology, we will 1) assemble a multi-layered spatio-temporal single cell roadmap to characterize and model how individual immune cells are affected by the TME in a murine model of GBM. 2) We will develop a computational framework for spatial transcriptomics to dissect single cells into niches defined by similar interaction programs with neighboring cells. 3) Using this tool, we will quantify the niche organization in human patients and identify ligand-receptor interaction pairs crucial for niche maintenance. 4) Candidate genes will be genetically ablated in either the tumor or the immune compartment and evaluated with regards to their in vivo efficacy in suppressing tumor growth. Our cutting-edge analytical pipeline from the identification of driver molecules for immune escape to the assessment of in vivo efficacy in a preclinical model of GBM will reveal novel targets for treatment. Our study thereby works directly towards the Horizon Europe Mission to understand, treat and beat cancer.

The European Consortium for Communicating Gene and Cell Therapy Information (EuroGCT) unites 49 partner organisations and institutions across Europe, including the major European advanced therapies learned societies, with the common goal of providing reliable and accessible information related to cell and gene therapy development to European stakeholders. EuroGCT has two major objectives: • To provide patients, people affected by conditions, healthcare professionals and citizens with accurate scientific, legal, ethical and societal information and with engagement opportunities, and thus to support better informed decision-making related to cell and gene-based therapies. • To facilitate better decision-making at key points in development of new therapies and thus enable improved product development, by providing the research community and regulatory and healthcare authorities with an information source on the practical steps needed for cell and gene therapy development. To achieve our aims, EuroGCT will adopt a highly structured system for coordinated management of information related to cell and gene therapy development and, from this, will implement an ambitious programme of online and direct stakeholder information provision and engagement. All outputs will be delivered in 7 European languages, to ensure broad accessibility, and will be rigorously evaluated against measurable objectives throughout the project duration. The proposed consortium comprises leading cell and gene therapy-related organisations and basic and clinical research labs across Europe, including new member states; together with experts in product development, ethical, legal and societal issues, and in evaluating clinical outcomes; patient representatives; and science communicators. It thus is uniquely placed to develop a world-leading cell and gene therapy information resource and to meet the challenge outlined in Topic SC1-HCO-19-2020.

Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time but continue to increase in diameter before they eventually rupture. Left untreated, the patients’ prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures can result in paraplegia from spinal cord ischaemia or even death, particularly for aneurysms extending from the thoracic to the abdominal aorta and thus involving many segmental arteries to the spinal cord, i.e. thoracoabdominal aortic aneurysms of Crawford type II. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10 to 20%. However, it has been found that the deliberate occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord does not increase rates of permanent paraplegia. A therapeutic option, ‘minimally invasive segmental artery coil embolization’ has been devised which proceeds in a ‘staged’ way to occlude groups of arteries under highly controlled conditions after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.