Project description DEENESFRITPL A double hit on cancer Cancer cells evolve a wide range of mechanisms to evade immune responses. Glioblastoma multiforme (GBM), the most aggressive brain tumour, is characterised by a highly immunosuppressive microenvironment that prohibits immunotherapy treatment. At the same time, tumour infiltration by myeloid-derived suppressor cells (MDSCs) further restrains both innate and adaptive immune responses. To address this issue, the EU-funded MHT-ImmunoEnhancer project proposes the development of a combinatorial treatment against GBM that encompasses hyperthermia to shrink the tumour alongside a strategy for depleting MDSCs. The intratumoural delivery of nanoparticles loaded with chemotherapeutic agents and immunomodulators is expected to induce regression of GBM tumours. Show the project objective Hide the project objective Objective Glioblastoma (GBM) is one of the most lethal and untreatable human tumours, and is characterized by its extremely poor prognosis. Conventional therapies, including surgery, radiotherapy and chemotherapy, have not resulted in major improvements in the survival, due to high recurrence and tumour spreading. Therefore, there is an urgent need to develop new effective therapies to improve patient survival. The establishment of an immunosuppressive tumour microenvironment (TME) in GBM is known to limit the cytotoxic effects of conventional therapies and in this context, myeloid-derived suppressor cells (MDSCs) play a critical role by promoting immune tolerance, tumour growth and spreading. Hyperthermal therapy in GBM has resulted in improved immune reactivity of tumours, despite this, its effectivity has been limited by its inability to overcome the immunosuppressive TME and induce strong systemic antitumour responses. Consequently, targeting MDSCs in combination with thermal ablation therapies appears to be a very promising strategy.The goal of the MHT-ImmunoEnhancer project is the development of a dual stimuli-responsive hybrid polymer/Iron oxide nanocubes (IONCs) delivery system in order to combine local fever-range Magnetic Hyperthermia (MHT) with MDSC depletion-targeted immunotherapy for intratumoral treatment of GBM. The specific objectives of our strategy are, 1) to exploit the superior heating efficiency of the hybrid polymer/IONCs platforms to induce tumour damage. 2) To turn the immunosuppressive TME into an immunosupportive one, by local delivery of CpG oligonucleotide; along with 5-Fluorouracil (5-FU), a chemotherapeutic agent. 3) To release CpG and 5-FU specifically at the tumour site under the appropriate stimulus (pH or enzymes/temperature), thus enhancing their tumour retention and therapeutic effect. All these actions will result in the reduction of T-cell-suppressive activity of MDSCs, enhancement of antitumour immune response and tumour regression. Fields of science medical and health sciencesclinical medicinesurgerynatural scienceschemical sciencespolymer sciencesmedical and health sciencesbasic medicineimmunologyimmunotherapynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes 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-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Net EU contribution € 183 473,28 Address VIA MOREGO 30 16163 Genova Italy See on map Region Nord-Ovest Liguria Genova Activity type Research Organisations 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 € 183 473,28
