A new approach to gene therapy using Sleeping Beauty to genetically modify clinical‐grade T cells to target CD 19

Summary The advent of efficient approaches to the genetic modification of T cells has provided investigators with clinically appealing methods to improve the potency of tumor‐specific clinical grade T cells. For example, gene therapy has been successfully used to enforce expression of chimeric antigen receptors ( CAR s) that provide T cells with ability to directly recognize tumor‐associated antigens without the need for presentation by human leukocyte antigen. Gene transfer of CAR s can be undertaken using viral‐based and non‐viral approaches. We have advanced DNA vectors derived from the Sleeping Beauty ( SB ) system to avoid the expense and manufacturing difficulty associated with transducing T cells with recombinant viral vectors. After electroporation, the transposon/transposase improves the efficiency of integration of plasmids used to express CAR and other transgenes in T cells. The SB system combined with artificial antigen‐presenting cells (a APC ) can selectively propagate and thus retrieve CAR + T cells suitable for human application. This review describes the translation of the SB system and aAPC for use in clinical trials and highlights how a nimble and cost‐effective approach to developing genetically modified T cells can be used to implement clinical trials infusing next‐generation T cells with improved therapeutic potential.