The CCRI has successfully managed to establish a wide network consisting of national and international partners collaborating with our scientists and clinicians at the St. Anna Children’s hospital on biomedical research projects and clinical studies for various childhood cancers. As a result, our predominantly charity-based organisation can gain access to and share the most recent cost-intensive technologies.
Establishing a zebrafish disease model drug screening platform (DANIO4CAN)
Project Coordinator: Dr. Martin Distel, Children´s Cancer Research Institute/Innovative Cancer Models
Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, AUT
Ludwig Boltzmann Institute for Cancer Research, AUT
Ce-M-M - Research Center for Molecular Medicine of the Austrian Academy of Sciences, AUT
Research Center for Molecular Medicine, AUT
University of Veterinary Medicine Vienna, AUT
Medical University of Vienna, Institute for Cancer Research, AUT
Zebrafish has been proven to be a cost-effective model organism to identify therapeutic strategies for human diseases. The Children’s Cancer Research Institute (CCRI) aims at upgrading its established zebrafish cancer and rare childhood disease model drug screening pipeline. Currently, small compounds are tested on zebrafish disease models in a time-consuming manual way with image acquisition being done on a confocal microscope. This bottleneck is preventing unbiased medium/high throughput screening of potential therapeutics. Acquisition of a zebrafish sorter able to automatically administer zebrafish larvae into 96 well plates and an automated system for high resolution image acquisition will lead to the establishment of a unique, powerful zebrafish drug screening platform in Austria accelerating European preclinical translational research and offering new opportunities in the development of precision medicine.
Funded under the programme R&D Infrastructure Funding, 1st call, by the Austrian Research Promotion Agency (FFG)
Duration: 01.05.2017 – 30.04.2019
Project Coordinator: Prof. Dr. Ruth Ladenstein , Children´s Cancer Research Institute/Studies and Statistics for Integrated Research and Projects
Ghent University Hospital, Hôpital Universiataire des Enfants Reine Fabiola, UZ Leuven, BEL
University Hospital Brno, University Hospital Motol, CZE
Copenhagen University Hospital, Rigshospitalet, DNK
Kuopio University Hospital, Tampere University Hospital, Turku University Hospital, the Hospital District of Southwest, FIN
Hôpital Bicetre, Hôpital Trousseau, Hôpital Universitaire Necker- Enfants maladies, Institut Curie, Institut d´hematologie et d´oncologie pédiatrique (IHOPE), Institut Gustave Roussy, Fondation Ophtalmologique Adolphe de Rothschild, FRA
Hannover Medical School, Dr von Hauner Children´s Hospital, University Hospital Munich, Charité Universitätsmedizin Berlin, Christian-Albrechts-Universität zu Kiel (CAU), Klinikum Dortmund GmbH, Klinikum Stuttgart-Olgahospital, University Children´s Hospital Tübingen, University Medical Center Freiburg, University Hospital Gießen- Marburg, University Hospital Bonn, DEU
Semmelweis University, HUN
Department of Pediatrics-University of Milano-Bicocca/Fundation MBBM, at San Gerardo Hospital, Monza, Istituto Giannina Gaslini, Meyer Children´s Hospital Florence, Ospedale Pediatrico Bambino Gesú, Policlinico San Matteo, Fondazione IRCCS Pavia, Azienda Ospedialiera di Padova (AOP), AziendaOspedaliera Universitaria Senese, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino- S.C. Oncoematologia Pediatrica e Centro Trapianti, Presidio Ospedale Infantile regina Margherita, Azienda Ospedaliera S. Maria della Misericordia di Perugia, ITA
Children´s Clinical University Hospital, Riga, LVA
Vilnius University Hospital Santariskiu Klinikos, LTU
Stichting VU-VUmc, Erasmus MC: Sophia Children´s Hospital, NDL
Copernicus Medical Company LTD, T. Maciniak Lower Silesian Specialist Hospital-Emergency Hospital,
University Children Hospital in Lublin (UCHL), University Clinical Center Gdansk, POL
Centro Hospitalar e Universitario de Coimbra, Instituto Português de Onclogia de Lisboa Francisco Gentil, EPE, PRT
University Medical Centre Ljubljana, SVN
Hospital de Sant Joan de Dèu, Hospital Universitari Vall d´ Hebron, Hospital Universitario y Politécnico La Fe Spain, Complejo Hospitalario Regional Virgen del Rocío, ESP
Karolinska University Hospital, Skâne University Hospital, SWE
Birmingham Children´s Hospital- NHS Foundation Trust, Great Ormond Street Hospital- NHS Foundation Trust, Royal Manchester Children´s Hospital, GBR
European Reference Networks are virtual networks involving healthcare providers across Europe. They aim to tackle complex or rare diseases and conditions that require highly specialised treatment and a concentration of knowledge and resources. There are 24 ERNS involving 25 European countries plus Norway, over 300 hospitals with over 900 healthcare units and covering all major disease groups.
The mission of the European Reference Network on Paediatric Cancer (ERN-PAEDCAN) is to improve outcomes of childhood cancer and malignant haematological diseases by reducing the current inequalities in different member states. Comparative population-based cancer registry research has provided robust evidence for significant inequalities in survival from childhood cancer across Europe: the difference may be as much as 30% units, with worse outcomes in Eastern Europe. Despite a reduction in the geographical differences in the period 2005–09, the former socialist economies still have roughly 20% excess mortality from cancer in children compared with the rest of Europe. The PaedCan ERN aims to provide paramount requirements for ‘Cross-border healthcare’ allowing the provision of healthcare to children with cancer in a Member State other than the Member State of affiliation. We identify target groups with conditions requiring a particular concentration of resources or expertise, especially when the expertise with certain cancer conditions is rare and case volume low. Taking into account the potential burden on families seeking cross border health care ERN-PAEDCAN intends to establish mechanisms to facilitate movement of information and knowledge rather than patients. We aim to extend local and national ‘tumour board’ culture to the cross border level with identified and required ICT tools and eHealth networks.
High-quality, accessible and cost-effective healthcare for childhood cancer are achieved by strengthening the integration of pre-existing knowledge and expertise, and fostering stronger cooperation between patients, professionals and healthcare authorities. The innovative contribution of ERN-PAEDCAN is a clear roadmap to approved expert referral sites and tumour advisory boards for healthcare providers fulfilling our vision of a more supportive environment for children with cancer with special needs by integrating pre-existing networks and knowledge across borders.
Funded under the 3rd Health Programme by the European Commission, call: HP-ERN-SGA-2016, Consumers, Health, Agriculture and Food Executive Agency (CHAFEA)
Duration: 01.03.2017 – 28.02.2022
Further information about the European Reference Networks: http://ec.europa.eu/health/ern/policy_en
Project Coordinator: Deutsches Krebsforschungszentrum (DKFZ), DEU
Prof. Dr. Heinrich Kovar , Children´s Cancer Research Institute/Molecular Biology of Solid Tumours,
Medizinische Universität Wien (MUW), AUT
Zürich University (UZH), Roche (ROCHE), CHE
Charité Berlin (Charite), Bayer AG (BAY), EPO-Berlin-Buch GmbH (EPO), Oncotest (OT), DEU
Fundació Sant Joan de Déu Barcelona (FSJD), PharmaMar (PHARMAMAR), ESP
European consortium for Innovative Therapies for Children with Cancer (ITCC), Institute Gustave Roussy (IGR), XenTech, Institut Curie (IC), FRA
Institute for Cancer Research (ICR), Eli Lilly and Co (Eli Lilly), Pfizer (PFZ), GBR
Alleanza Contro il Cancro (ACC), ITA
Academic Medical Center (AMC), Prinses Maxima Center Utrecht (PMC), NDL
Cancer remains the leading cause of disease-related death in children. For the ~25% of children who experience relapses of their malignant solid tumors, usually after very intensive first-line therapy, curative treatment options are scarce. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the facts that i) molecular genetic data on pediatric solid tumors from relapsed patients and thus our understanding of tumor evolution and therapy resistance are very limited to date and ii) for many of the high-risk entities no appropriate and molecularly well characterized patient-derived models and/or genetic mouse models are currently available. Thus, quality-assured upfront preclinical testing of novel molecularly targeted compounds in a (saturated) repertoire of well-characterized models will establish the basis to increase therapeutic successes of these drugs in children with solid malignancies. Since these tumors are overall genetically much less complex than their adult counterparts, it is anticipated that it will be easier to identify powerful predictive biomarkers to allow for accurate matching of targets and drugs.
To address this high, as yet unmet clinical need, we have formed the ITCC-P4 consortium consisting of academic and commercial partners from 8 European countries and covering the full spectrum of qualifications needed for quality-assured preclinical drug development including expertise in patient derived models, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, medical expertise regarding the entities in question, regulatory knowledge, and project management of large consortia.
With this consortium in a public-private partnership with the participating pharma companies we strongly believe to be ideally positioned to greatly expedite the development of more precise and efficacious drugs for children with malignant solid tumors.
Funded under the programme Innovative Medicines Initiative, call H2020-JTI-IMI2-2015-07, by the European Commission
Duration: 01.01.2017 – 31.12.2021
Project Coordinator: Assoc. Prof. Dr. Peter Ambros, Children´s Cancer Research Institute/Solid Tumours
Institut Curie Département d'Oncologie Pédiatrique et INSERM U830, Paris, FRA
Charité - Universitätsmedizin Berlin, Department of Pediatric, Berlin, DEU
Deutsches Krebsforschungszentrum DKFZ, Department of Neuroblastoma Genomics, Heidelberg, DEU
Ghent University Center for Medical Genetics, CMGG, Gent, BE
Neuroblastoma (NB) is the most devastating solid tumour in childhood. Extensive clinical/translational research has led to valuable prognostic classifiers for risk-adapted therapy, but intratumour genetic heterogeneity (ITH) limits the accuracy of classifiers generated from single biopsies of bulky tumours. Spatial/temporal ITH is a major obstacle to effective treatment and the true extent has only recently been hinted at by progress in sequencing technology. Highly sensitive, precise molecular diagnostic tools are needed to detect the relapse seeding clone and (sub)clonal mutations conferring therapy resistance. The entire spectrum of druggable gene mutations involved in resistance and relapse must be identified to make use of the increasing availability of drugs specifically targeting mutated genes. ONTHETRRAC joins expertise of the leading investigator-driven European NB clinical trial groups, SIOPEN and GPOH, with the goal of innovative ITH assessment in preclinical models and patient samples, application of new diagnostics and treatment algorithms targeting ITH in clinical trials.
Analyses of tumour tissue and liquid biopsies by advanced genomic, expression and epigenomic techniques will generate a more complete picture of spatial/temporal ITH and support an individualised therapeutic strategy based on the most aggressive and druggable tumour clone. Minimally invasive techniques will support monitoring for point mutations and disease load.
Development of new strategies to overcome tumour sampling error based on ITH, including i) establishing techniques to detect resistant clones in tumour tissue/liquid biopsies, ii) performing a systematic combined analysis of genomic/RNA/epigenetic changes in primary/metastatic patient samples, iii) establishing a robust technique for disease monitoring and detection of druggable mutations, iv) validating biomarkers in biological models and v) providing recommendations for the best strategies to molecularly diagnose/monitor disease for implementation into the next high-risk/relapse NB trial protocol.
The ONTHETRRAC consortium combines translational researchers with solid backgrounds in NB and specific expertise in whole genome/exome sequencing (WGS/WES), bisulfite sequencing, RNAseq, ChIPseq, miRNA and ncRNAs analyses, single-cell analyses and cell enrichment techniques.
Expected results & potential impact: ONTHETRRAC will advance understanding of molecular ITH in NB and firmly establish ITH issues in current diagnostic procedures and disease monitoring to enable the design of more effective treatment strategies taking all facets of the malignancy into account. The bundled unique expertise within ONTHETRRAC is best positioned to explore and validate relevant NB biomarkers and narrow the gap between understanding ITH in NB and applying current clinical methods for response and resistance with precision medicine approaches.
Funded under the European ERA-NET programme TRANSCAN-2, Austrian Science Fund (FWF)
Duration: 01.01.2016 – 30.09.2018
ERN-PAEDCAN Partner: Paediatric Rare Tumours Network - European Registry
Project Coordinator: Azienda Ospedaliera di Padova, ITA
Prof. Dr. Ruth Ladenstein , Children´s Cancer Research Institute/Studies and Statistics for Integrated Research and Projects, AUT
Klinikum Dortmund GmbH, DEU
Eberhard Karls Universität Tübingen, DEU
Institut Curie, FRA
Gdanski Uniwersytet Medyczny, POL
National registries dedicated to collect epidemiological, clinical and treatment data of children and adolescents with very rare tumours (VRT) exist in four European countries: France, Germany (including Austrian patients), Italy and Poland. Aim of this project is the creation of a Paediatric rare tumour European Registry (PARTNER) linking the existing national registries. PARTNER will be also linked to a virtual consultation system, a dedicated website and the elaboration of diagnostic/
Strategic relevance: The value of this project is based on the European wide gathering of information on treatment of VRT and the provision of this information to experts generating new guidance recommendations for daily practice. The platform that will be created using innovative IT tools to link the existing databases will enhance European collaboration and facilitate cross border access to dedicated expertise.
Methods and means: The first step will be a process of harmonization of the national registries, (identification of the VRT of interest, selection of variables, use of common definitions and procedures for data management) and discussions of the regulatory issues relevant for the different countries. PARTNER will be then created and linked to the existing registries through the adoption of EUPID, a privacy-preserving, secure and versatile system for pseudonymised patient registration and record linkage. Standard of care recommendations will be also elaborated by a dedicated Working Group. LHEAR countries will be involved in the whole of process creating the basis for a larger EU registry and facilitating recommendations dissemination.
Expected outcome: This project will lead to the creation of a comprehensive EU platform that can be easily accessed by EU Health care providers and will ultimately result in improved patients’ care and reduction of the existing inequalities in cancer outcome across EU member states.
Funded under the 3rd Health Programme, call HP-PJ-06-2016 (Rare diseases – support for New Registries), by the European Commission
Duration: 01.01.2018 – 31.12.2020
Platform supporting an integrated analysis of image and multiOMICs data based on liquid biopsies for tumor diagnostics (VISIOMICS)
Project Coordinators: Dr. Sabine Taschner-Mandl and DI Florian Kromp , Children´s Cancer Research Institute/Solid Tumours.
The project is conducted by the fully owned subsidiary of the CCRI, Labdia Labordiagnostik GmbH
Research Studios Austria Forschungsgesellschaft, Vienna, AUT
Software Competence Center Hagenberg GmbH, Upper, Austria, AUT
Platomics GmbH, Vienna, AUT
CogVis Software und Consulting GmbH, Vienna, AUT
VRVis Zentrum für Virtual Reality und Visualisierungs-GmbH, Vienna, AUT
Universitätsklinikum Erlangen, Hautklinik, Erlangen, DEU
VISIOMICS aims at developing a comprehensive solution for refined tumor diagnostics offering workflow management, multi-level data integration and advanced user interface solution in one efficient and certifiable workflow.
Neuroblastoma, as a rare disease, will serve as a model to help solving the currently frequently observed problems in diagnostics accompanying personalized treatment strategies, i.e. integration of multi-level data despite of scarcity of samples and incomplete datasets.
We therefore plan to expand our analysis by integrating DNA/RNA-sequencing and SNP-array data and combine them with imaging derived morphological and antibody staining properties of disseminated tumor cells isolated from liquid biopsies.
Integration is performed in a sequential manner to better define genes and/or cell features, allowing to distinguish between samples from relapse versus non-relapse patients already at the time of diagnosis.
The VISIOMICS software platform, linked to a centralized database storing raw and processed data, will be an important tool enabling efficient user interaction and data visualisation tasks to translate expert knowledge into clinical/diagnostic analysis workflows.
Funded under the programme COIN “Netzwerke” (tender 9) by the Austrian Research Promotion Agency (FFG)
Duration: 01.11.2017 – 31.10.2019
Project Coordinator: Technische Universität Wien, AUT
Prof. Dr. Michael Dworzak , Children´s Cancer Research Institute/Immunological Diagnostics
Charité – Universitätsmedizin Berlin, DEU
CogVis Software and Consulting GmbH, AUT
Informations- und Kommunikationsgesellschaft mbH, DEU
Project summary, results and future outlook:
Acute Lymphoblastic Leukaemia is the most frequent leukaemia entity in children and adolescents. Despite continued progress and refinement of therapeutic approaches, disease relapse due to insufficient extinction of leukaemic blasts still remains the number one cause of treatment failure. About 15-20% of paediatric patients with the disease still suffer from relapse. Flow cytometry (FCM) is one of the methodologies most useful in this respect, because it is widely available and applicable to most patients. While sample preparation, antibody panels, staining procedures, and FCM acquisition can be harmonized straightforwardly, data analysis and interpretation rely largely on operator skills and experience. These assessments are time-consuming and costly to be attained via staff-training, online support between twinning laboratories, and continued quality control. Hence, these requirements represent the current bottleneck of safely applying the FCM Minimal Residual Disease (MRD) methodology in a growing community of diagnostic laboratories to the benefit of an increasing number of patients with leukaemia.
To address this bottleneck, AutoFLOW aims at developing an objective and automated tool for multi-parameter FCM data analysis with robust and reliable MRD quantification. The consortium engages professionals from the medical and ICT fields in a network where the exchange of knowledge culminates in a valid solution for automated FCM analysis for clinical follow-up assessment of Acute Lymphoblastic Leukaemia (ALL).
Showing the success of this project, the software “FLOWVIEW” was already developed and is available for testing on the AUTOFLOW website (link below). FLOWVIEW is based on the powerful algorithms and database of expert-evaluated FCM records. Users can upload FCM files, perform a fully automated gating procedure (duration so far <90sec.) to describe populations of healthy and blast cells, currently with a precision of >90% so far, but with a growing number of special ALL variants this figure will improve. FlowVIEW can visualise 20 (actually up to 120) different plots of a cell sample with up to 2 million data points in real time, i.e. the user is able to zoom in in each plot and consider each cell population in detail. This is possible because the processes are calculated directly on the graphics card and therefore very large amounts of data such as the FCM output can be processed quickly.
To improve and standardize quality-assured MRD-assessment necessary for proper treatment selection upon assessment of leukaemic response parameters, the AUTOFLOW team allows dissemination of automated FCM-MRD analysis to medical centres which have no established expertise – for the benefit of diseased children with ALL.
Funded under the Seventh Framework Programme (FP7-PEOPLE-2013-IAPP) by the European Commission
Duration: 01.01.2014 – 31.12.2017
Project Coordinator: Prof. DDr. Thomas Lion, Children´s Cancer Research Institute/Molecular Microbiology
Medizinische Universität Wien (MUW), AUT
Fraunhofer Gesellschaft zur Förderung der Angewandten Forschung e. V., DEU
University of Tuzla, BIH
Molzym GmbH & Co. KG, DEU
Genedata AG, CHE
Project summary, results and future outlook:
Invasive fungal disease (IFD) is a leading cause of morbidity and mortality in the growing number of immunocompromised individuals, including particularly cancer patients, and bone-marrow or organ transplant recipients. Timely pathogen detection is a prerequisite for effective therapy in patients with IFD. FUNGITECT focuses on this medical priority and the plan is to develop, validate and market a specific set of novel molecular diagnostic tests for IFD targeting fungal DNA-, RNA- and protein motifs, as well as the enzymatic activity of fungal pathogens. Additionally, FUNGITECT provides a unique opportunity to establish and implement highly effective diagnostic assays supported by Next-Generation Sequencing and a bioinformatics service platform, facilitating optimized treatment strategies adapted to individual patient requirements.
The establishment of a first line of rapid and inexpensive diagnostic tools based on standardized and validated assays including a) panfungal RQ-PCR, b) monoclonal antibody arrays, c) biochips detecting fungal enzymatic activity, and/or d) optimized PCR-based sequencing will permit rapid clinical implementation due to the low-costs and point-of-care applicability. For a second line of advanced fungal diagnostics, FUNGITECT will place particular emphasis on the development and exploitation of NGS-based technologies offering unprecedented diagnostic options for highly effective management of complex infectious diseases such as IFD.
The economic impact of implementing effective fungal diagnostics, as proposed in this project, is expected to be very significant. With the accurate diagnostic procedures introduced by FUNGITECT, the efficiency in the management of invasive fungal diseases will provide an economic landmark. It could represent the beginning in the inversion of the cost escalation inherently related to inadequate diagnostic methods resulting in suboptimal patient management often leading to significant overtreatment. In addition to expected benefits regarding the future economic development of the participating SMEs, the entire field of fungal diagnostics can profit from the new diagnostic possibilities. The FUNGITECT consortium will contribute to achieving durable integration in the European Research Area and to fostering European competitiveness and excellence.
Funded under the Seventh Framework Programme (FP7-HEALTH-2013-INNOVATION-1) by the European Commission
Duration: 01.01.2014 – 31.12.2017