Project description DEENESFRITPL A 3D snapshot of antigen recognition could pave the way to enhanced immunotherapy Cancer immunotherapy is gaining a lot of interest for its potential to boost a person's own immune system to attack tumours, but treatment efficacy and patient response have so far been unpredictable. Among the most important cells in the immune system are the T-cells that mediate adaptive immunity via their T-cell receptors (TCRs). TCRs recognise invaders from small molecules (peptides) presented to them by so-called antigen-presenting cells via major histocompatibility complex (MHC) proteins. This process is extremely specific in vivo and harnessing this specificity could provide a breakthrough in immunotherapy. The EU-funded TCRabX project is using high-tech methods to study the detailed 3D structures of TCRs bound to MHC proteins to identify the TCR contact regions. Show the project objective Hide the project objective Objective Demographic change includes population ageing, and incidence rates begin to increase for many types of cancer in middle-aged and elderly people. Traditional cancer treatment includes surgery, chemotherapy, and radiation therapy, while tumour immunotherapy by T cell receptor (TCR) gene transfer represents an alternative form of treatment. The transfer of tumour-specific TCR genes into patient’s peripheral blood lymphocytes targets cancer specifically and effectively. But while patient-derived low-affinity TCRs do not show therapeutic activity, optimal-affinity TCRs, as isolated from newly-generated antigen-negative humanized mice with a diverse human TCR repertoire, can effectively delay tumour regression. X-ray crystallography is a powerful tool of structural biology, which helps researchers to identify the three-dimensional (3D) structures of biological macromolecules such as TCRs complexed to their cognate peptide-loaded major histocompatibility complex (pMHC) molecules. Recent research uncovered the docking topologies of naturally selected TCRs, but therapeutically efficient optimal-affinity TCRs recognizing tumour-associated self-antigens, have not been analysed to date. The exceptional specificity of TCRs is determined by three complementarity-determining regions (CDRs) of the TCR alpha- and beta-chains. Biomedical research on TCR gene therapy and design of future clinical trials will hugely benefit from the identification of CDR-mediated contact points made between therapeutic TCRs and the pMHC on their target cells. TCRabX is an interdisciplinary research project investigating the 3D structures of 13 TCRs complexed to MHC-I or MHC-II, respectively. It connects innovative clinical immunology research in Berlin/Germany and world-class structural biology research in Melbourne/Australia. The proposed research will enhance the health and well-being of citizens in Europe and worldwide by supporting the advancement of cancer immunotherapy approaches. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesclinical medicinesurgerymedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator CHARITE - UNIVERSITAETSMEDIZIN BERLIN Net EU contribution € 264 110,40 Address Chariteplatz 1 10117 Berlin Germany See on map Region Berlin Berlin Berlin Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 264 110,40 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. MONASH UNIVERSITY Australia Net EU contribution € 0,00 Address Wellington Road 3800 Victoria See on map Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 178 380,00
