title: A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19.
abstract: 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.
authors: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Harjeet
authors: H
authors: Singh
authors: Helen
authors: H
authors: Huls
authors: Partow
authors: P
authors: Kebriaei
authors: Laurence J N
authors: LJ
authors: Cooper
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology*; D018929:Cell Culture Techniques; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D059765:Homologous Recombination; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018941:Antigens, CD19; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell
keywords: Sleeping Beauty; T cells; adoptive immunotherapy; gene therapy; transposase CD19; transposon