A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19.

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 (CARs) that provide T cells with ability to directly recognize tumor-associated antigens without the need for presentation by human leukocyte antigen. Gene transfer of CARs 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 (aAPC) 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.

Singh H ，Huls H ，Kebriaei P ，Cooper LJ ... -  《-》

Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells.

Singh H ，Figliola MJ ，Dawson MJ ，Olivares S ，Zhang L ，Yang G ，Maiti S ，Manuri P ，Senyukov V ，Jena B ，Kebriaei P ，Champlin RE ，Huls H ，Cooper LJ ... -  《PLoS One》

Clinical application of Sleeping Beauty and artificial antigen presenting cells to genetically modify T cells from peripheral and umbilical cord blood.

Huls MH ，Figliola MJ ，Dawson MJ ，Olivares S ，Kebriaei P ，Shpall EJ ，Champlin RE ，Singh H ，Cooper LJ ... -  《Jove-Journal of Visualized Experiments》

Generation of CAR+ T Lymphocytes Using the Sleeping Beauty Transposon System.

Chicaybam L ，Abdo L ，Bonamino MH 《-》

Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells.

Kebriaei P ，Singh H ，Huls MH ，Figliola MJ ，Bassett R ，Olivares S ，Jena B ，Dawson MJ ，Kumaresan PR ，Su S ，Maiti S ，Dai J ，Moriarity B ，Forget MA ，Senyukov V ，Orozco A ，Liu T ，McCarty J ，Jackson RN ，Moyes JS ，Rondon G ，Qazilbash M ，Ciurea S ，Alousi A ，Nieto Y ，Rezvani K ，Marin D ，Popat U ，Hosing C ，Shpall EJ ，Kantarjian H ，Keating M ，Wierda W ，Do KA ，Largaespada DA ，Lee DA ，Hackett PB ，Champlin RE ，Cooper LJ ... -  《-》