A microRNA-regulated cell death-inducing gene therapy for T-cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Although outcome has improved throughout the years with the use of combined chemotherapy, the aggressive regimens required for treatment efficacy often lead to significant short- and long-term side effects. Moreover, a significant fraction of T-ALL patients relapse, which have extremely poor prognosis. The current project aligns with the core goal of our ERC Consolidator Grant IL7sigNETure (CoG-648455) to generate new targeted therapies for improved treatment of T-ALL, by aiming to develop a gene therapy cell death-inducing system (miRTo) that uses cell-endogenous microRNAs to regulate the expression of a cell death-inducing gene specifically in T-ALL cells (miRToTALL). While our innovative strategy has the potential to treat T-ALL patients more effectively and safely, it also displays market potential that extends well beyond T-ALL. This is because our technology is designed so that it can be adapted to the disease of choice or to particular disease subtypes through simple modifications, making it ideal for precision medicine in T-ALL, other cancers or other indications in which patients may benefit from the targeted delivery of a therapeutic gene. Our project will build upon the preliminary data that we have already generated, and make use of our models and expertise in the molecular and cellular biology of T-ALL, to provide preclinical validation of miRToTALL, laying the ground for a spin-off that will fully explore the miRTo technology platform.