Project description DEENESFRITPL Double blow on neuroblastoma Immunotherapy is a promising anticancer strategy in principle, but clinical results show great variation among different types of cancer. The immunosuppressive tumour microenvironment seems to hinder the efficacy of various regimens, including engineered chimeric antigen receptor T cells. Funded by the Marie Skłodowska-Curie Actions programme, the IronKiller project proposes to combine a natural killer (NK)-based immunotherapy with drugs that activate ferroptosis to treat refractory neuroblastoma. Ferroptosis is a cell death mechanism that activates the immune system and recruits NK cells. Moreover, researchers will develop a modelling approach for predicting the outcome of such combinatorial treatment in individual patients. Show the project objective Hide the project objective Objective Neuroblastoma (NB), a rare paediatric solid tumour, accounts for 15% of childhood cancer deaths. Immunotherapy has improved the survival for haematological malignancies, but solid tumours remain a challenge. The high heterogeneity, low mutational load, and strong immunosuppressive tumour microenvironment (i-TME) have hindered the success of immunotherapy in NB. Recently, natural killer (NK) cells have stood as a promising immunotherapeutic tool, as they don’t depend on specific mutations. Still, clinical trials for NB show only modest results, proving further action is needed to overcome the iTME. Late findings show that refractory tumours often respond to Ferroptosis, a novel cell death mechanism that is highly immunogenic. Cancer cells undergoing ferroptosis release HMGB1 and other well-known recruiters of NK cells. Moreover, ferroptotic drugs can act through several mechanisms and can be adapted to patients with different tumour characteristics. The goal of IronKiller is to combine ferroptotic drugs with NK cell therapy to treat refractory NB, and to perform in silico modelling of the results to predict which patients would benefit from this novel therapy.I am an experienced biologist and engineer joining a clinical research group strong in immunotherapies. We will follow an in vitro-in vivo-in silico strategy that will cover a variety of disciplines, from basic biology and pre-clinical research, all the way to bioinformatics and machine learning. I will reinforce my experience in cell death mechanisms and translational research, and I will also acquire new knowledge and skills in the areas of cell immunotherapy and oncological mathematical modelling. The latter through a secondment at an academic institution. Along with the research work, the diverse training, management and communication activities planned, will play a key role in advancing my professional development towards becoming an independent academic group leader in translational cancer research. Fields of science natural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesmedical biotechnologycells technologiesnatural sciencesmathematicsapplied mathematicsmathematical model Keywords neuroblastoma ferroptosis natural killer cells immunotherapy mathematical modelling Programme(s) HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme Topic(s) HORIZON-MSCA-2021-PF-01-01 - MSCA Postdoctoral Fellowships 2021 Call for proposal HORIZON-MSCA-2021-PF-01 See other projects for this call Funding Scheme HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships Coordinator FUNDACION PARA LA INVESTIGACION BIOMEDICA DEL HOSPITAL UNIVERSIATRIO LA PAZ Net EU contribution € 165 312,96 Address PASEO DE LA CASTELLANA 261 28046 Madrid Spain See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Other Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost No data Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSIDAD DE CASTILLA - LA MANCHA Spain Net EU contribution € 0,00 Address CALLE ALTAGRACIA 50 13071 Ciudad Real See on map Region Centro (ES) Castilla-La Mancha Ciudad Real 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 No data
