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.
Original language | English (US) |
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Pages (from-to) | 181-190 |
Number of pages | 10 |
Journal | Immunological Reviews |
Volume | 257 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2014 |
Keywords
- Adoptive immunotherapy
- Gene therapy
- Sleeping Beauty
- T cells
- Transposase CD19
- Transposon
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
MD Anderson CCSG core facilities
- Monoclonal Antibody Facility