Objectif Recent encouraging clinical results obtained with engineered T lymphocytes and increasing advances in the genome editingfield, have opened new opportunities for T-cell receptor (TCR) gene therapy as an immunotherapeutic approach for cancer.Unfortunately, the broad applicability of this treatment is still hampered by the possible mispairing of exogenous/endogenousTCR chains and by the limited number of high avidity tumor-specific TCRs. While the first issue has been successfullyaddressed by the hosting lab with the development a TCR gene editing protocol, the identification of novel tumor-specificTCRs is urgently required and this is the aim of my research proposal. We have the unique opportunity to combine the highlycomplementary expertise of the hosting lab in T-cell biology/genetic transfer and of the applicant on immune repertoiresequencing. We will target acute myeloid leukemia (AML) and hypothesize that by exploiting intrinsic features of AML (i.e.ability of AML blasts to differentiate into potent antigen presenting cells expressing tumor antigens), the functional fingerprintinduced by AML on tumor-reactive T-cells, and cutting-edge technologies (i.e. next generation sequencing; ligandomelandscape analysis), we will provide a comprehensive immunoprofiling of tumor-specific T-cells and isolate tumor TCRspecificities. Results obtained in this study will streamline TCR hunting studies in solid tumors, leading to the generation of aTCR library for different antigens and HLA restrictions, thus rendering TCR gene editing an innovative off-the-shelftreatment available for a high number of cancer patients. Awarding this fellowship will greatly enhance researcher’s careernot only by providing the opportunity to widen scientific knowhow and acquire new skills, but also by enabling the researcherto address a major bottleneck currently limiting the full exploitation of the rapidly growing field of cancer immunotherapy. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesclinical medicineoncologyleukemianatural sciencesbiological sciencesgeneticsgenomes 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 Thème(s) MSCA-IF-2016 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2016 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-SE - Society and Enterprise panel Coordinateur OSPEDALE SAN RAFFAELE SRL Contribution nette de l'UE € 168 277,20 Adresse VIA OLGETTINA 60 20132 Milano Italie Voir sur la carte Région Nord-Ovest Lombardia Milano Type d’activité Private for-profit entities (excluding Higher or Secondary Education Establishments) Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 168 277,20
