Objective 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. Fields of science 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 Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-SE - Society and Enterprise panel Coordinator OSPEDALE SAN RAFFAELE SRL Net EU contribution € 168 277,20 Address VIA OLGETTINA 60 20132 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding 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 € 168 277,20