Impact of Treatment With Targeted Therapies on the Generation of CAR T Cells in CLL Patients

This is a biological study aimed at analyzing the features of CAR T cells generated in CLL patients treated with ibrutinib or venetoclax. To this purpose, blood samples will be collected from patients with CLL before starting therapy with ibrutinib or venetoclax and after 6 and 12 months of treatment. Anti-CD19 CAR T cells will be generated and tested for: (i) viability, expansion and generation efficiency; (ii) phenotypic characteristics, in terms of CD4/CD8 composition, differentiation subset distribution, exhaustion markers and expression of immune checkpoint molecules; (iii) in vitro functional properties, in terms of proliferation ability, cytokines production, cytotoxic activity and killing of target cells. CAR T cells produced from the same patient at different timepoints will be compared. Phenotypic and functional data on CAR T cells will be also correlated with main CLL prognostic factors (e.g. IGHV mutational status, FISH abnormalities, TP53 mutation status) and outcome variables (response status, duration of response).