Linking outcome of CD19-directed CAR T cell therapy with genome modification by vector integration

Chimeric antigen receptor-engineered T-cells targeting CD19 (CART19) provide a highly effective treatment for pediatric acute lymphoblastic leukemia (ALL) but are less effective for chronic lymphocytic leukemia (CLL) and other indications, focusing attention on approaches to improve efficacy. CART19 cells are prepared by integration of the engineered receptor gene into the host T cell chromosome using a lentiviral vector. Vector integration thus marks T cell lineages uniquely and modifies the cellular genome by insertional mutagenesis. We investigated clonal population structure and therapeutic outcome for 40 subjects by high throughput sequencing of sites of vector integration. Sequences captured by the INSPIIRED protocol are deposited here for analytical reproduction and further investigations.