Adoptive therapy with T cells that were modified with gamma-retroviral and lentiviral (LV) vectors to express a CD19-specific chimeric antigen receptor (CAR) has shown remarkable efficacy in pilot clinical trials. However, there are persistent concerns with the use of viral vectors with regard to safety, as well as the cost and scale of vector production required for making CAR T-cell therapy available to patients on a global level. In this study, we have refined non-viral Sleeping Beauty (SB) transposition to provide an effective and broadly applicable gene-transfer strategy with superior safety profile.