Brenner D.,Luxembourg Institute of Health |
Blaser H.,Ontario Cancer Institute |
Mak T.W.,Ontario Cancer Institute |
Mak T.W.,University of Toronto
Nature Reviews Immunology | Year: 2015
Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that has important roles in mammalian immunity and cellular homeostasis. Deregulation of TNF receptor (TNFR) signalling is associated with many inflammatory disorders, including various types of arthritis and inflammatory bowel disease, and targeting TNF has been an effective therapeutic strategy in these diseases. This Review focuses on the recent advances that have been made in understanding TNFR signalling and the consequences of its deregulation for cellular survival, apoptosis and regulated necrosis. We discuss how TNF-induced survival signals are distinguished from those that lead to cell death. Finally, we provide a brief overview of the role of TNF in inflammatory and autoimmune diseases, and we discuss up-to-date and future treatment strategies for these disorders. © 2015 MacmillanPublishers Limited. Source
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-2 | Award Amount: 3.91M | Year: 2008
In clinical studies, proteomics and transcriptomics allow the comparison of samples from different patients and hold special promise for the discovery of novel biomarkers and the development of personalized medicine approaches. Yet, translating recent discoveries into daily medical practice takes time and despite intensified researchers interest and investments, the rate of introduction of novel biomarkers in clinical practice is extremely disappointing. The main aim of DECanBio is to implement a strategy for protein biomarker discovery and validation relying on the use of state of the art mass spectrometry instrumentation for quantitative analysis of proteins. For the first time, the potential of MRM-Mass Spectrometry (MRM-MS) will be tested in the scope of a large scale validation protocol of cancer protein biomarkers. This analysis will be performed in parallel to the application of miniaturized high-throughput ELISA tests for protein quantification. DECanBio strategy will be applied to issues related to bladder cancer. Specifically, a restricted number of urinary protein biomarkers enabling the detection of recurrences during the monitoring period of patients treated for bladder tumour will be validated. The work will be performed in priority for the follow-up of low-grade superficial bladder tumours (Ta stage), which, after initial resection (without BCG therapy), are likely to evolve towards remission, recurrence, or progression to a high-grade tumor. The MRM and ELISA tests developed herein aim at the high-throughput quantification of these markers in urine. Collectively, the project has the ambition to settle a whole experimental pipe-line, from the search for new bladder cancer biomarker candidates, to their thorough evaluation and validation in clinical environment. We anticipate that the tools and knowledge that will be developed here will greatly facilitate translational studies for other diseases as well.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.0-1 | Award Amount: 5.06M | Year: 2013
FLUTCORE will develop a novel universal influenza A virus (IAV) vaccine based on the tandem core vaccine platform. Recent influenza pandemics have emphasized the urgent need for better vaccines that are reactive with multiple IAV subtypes and that are no longer dependent on intimate knowledge of the prevalent virus. We propose to replace the existing seasonal IAV vaccine with a virus like particle (VLP) carrying several invariant universal influenza antigens. Previous attempts to use these targets have failed due to the poor antigen expression and immunogenicity. The highly immunogenic tandem core system overcomes this limitation. Specifically, we propose to develop a VLP carrying two or more invariant influenza antigens, express these in yeast and then examine immunogenicity in mice. The vaccine will be further tested in the rigorous ferret system before being scaled up for manufacture. An optimal clone will then be transferred to an accredited contract manufacturer for production. A phase I clinical trial will be carried out once pre-clinical toxicology has been successfully completed. Our consortium will examine the immune responses in both animals and humans thoroughly to ensure that the vaccine candidate chosen can produce a protective IAV immune response in all individuals. To achieve these objectives, our proposal builds upon the complementary expertise of seven high-performing partners representing four European countries, with world leadership in HBV core biology, immunological analysis, commercial manufacture and influenza clinical trials, making our consortium ideally positioned to develop the vaccine and to take it from bench to bedside. The leading role of SMEs in the consortium will ensure that the technology developed by FLUTCORE will generate highly marketable products, offering both improved patient protection and long-term cost savings for health care in Europe once annual influenza vaccines are replaced.
Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2010-IRSES | Award Amount: 354.90K | Year: 2011
1.6 million people are killed worldwide each year due to ovarian, endometrial, bladder and prostate cancers. The key to making treatment breakthrough is early diagnosis. PROTBIOFLUID is a new network for developing innovative early diagnostic techniques and for spreading this knowledge through the medical community by a systematic exchange of staff to create high impact benefits to patients and transform the way these cancers are managed. Our overall science objective is to study biofluids in cancer patients in order to determine specific proteomic profiles to lay the foundation for the development of a simple to use diagnostic tool that will become ubiquitous in the medium-to-long-term. Our objectives to create this impact are: 1. Establish new methods for proteomic identification of biomarkers in biofluids for the early diagnosis and prognosis of cancer 2. Evaluate molecular markers and therapeutic targets of metastasis through the use of preclinical animal models Currently the know-how to reach these objectives exists but the field is highly fragmented. Therefore, we need this IRSES project as a catalyst for a focused network to create the critical mass to solve very pressing treatment problems. We have selected leading research partners with established relations of trust and reciprocity and who bring the correct combinations of complementary expertise. To effect the interlinking of research lines we have designed a systematic exchange of both very senior staff and those at earlier phases of their career. Through this mechanism we will achieve both high level knowledge exchanges as well as knowledge transfer through teaching and hands on experience of best practice. At the end of the PROTBIOFLUID we will have agreed a framework for joint programming between partner institutions. This first nucleus of teams will be the core of a growing network of excellence that will transform both what and how things are done in the treatment of these deadly cancers
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.4.2-3 | Award Amount: 3.65M | Year: 2013
There exist more than 7000 rare diseases worldwide and the European Society of Paediatric Oncology stated that 75% of rare diseases affect children and 30% of rare disease patients die before the age of five. Usual statistical methods for proving efficacy and safety of therapies fail to provide cost-efficient and reliable results in small populations. There is a pressing need to integrate a broad range of innovative methodologies improving clinical trials in the setting of small sample population groups (SPG). The objective of this research is to produce methods of general applicability irrespective of indication by Integrated DEsign and AnaLysis of clinical trials in SPG (IDEAL) through a multidisciplinary closely collaborating consortium of researchers from European universities, research institutes and industry. The consortium will work in 10 WPs, focussed on assessment of randomization procedures, extrapolating dose-response information, investigation of adaptive designs, optimal designs in mixed models, pharmacogenetic designs, simulation of clinical trials, genetic factors influencing the response, decision analysis and biomarker surrogate endpoints as well as WPs on project management and dissemination of results. Relevant stakeholder concerns (patient needs, regulatory issues, reimbursement, clinical feasibility) will be monitored by a Clinical Scientific Advisory Board. Because of its integrative structure, this research program extends previous approaches, which focus on a certain methodology only. In its totality, the WPs constitute a logically coherent set of methodologies that is of sufficient breadth to tackle these important, multidisciplinary challenges. By combining, enhancing and developing different statistical methodologies and assessment methods, this research program will impact the scientific discussion in promoting efficient statistical methodology for clinical trials in SPG, also in view of existing regulatory guidance in the EU.