Uncover and overcome senescence and dysfunction of genetically engineered T lymphocytes for cancer immunotherapy
Progetto Our ultimate objective is the development and validation of biotechnological tools, to be combined by a modular approach, to
generate innovative T-cell based advanced medicinal products for the treatment of acute myeloid leukemia (AML), a major
unmet clinical need. We shall exploit our toolbox of genome editing and gene transfer reagents to endow engineered T cells
to: i.Specifically recognize peptide and lipid antigens relevant for oncogenesis and tumor progression; ii.Display a memory
stem T cell (TSCM) phenotype which is associated to cell fitness, iii.Counteract the immunosuppressive tumor
microenvironment (TME), through the permanent disruption of inhibitory receptor genes. However, long-term persistence
and efficacy of gene-modified T cells is limited by cellular stress responses and senescence inadvertently triggered by the
multiple steps of genetic manipulation. Here, we aim at unveiling and overcoming these detrimental programs in advanced
cellular products for AML treatment.