The administration of ex vivo engineered T cells is championed by academia and industry alike and has resulted in dramatic clinical responses. I will discuss how T cells can be engineered ex vivo using a transposon/transposase system for in vivo applications. We will discuss how this non-viral approach to gene therapy can be combined immunotherapy to redirect specificity and improve the effector functions of T cells manufactured for clinical trials. For example, T cells can be genetically modified to express chimeric antigen receptors (CARs) and T-cell receptors (TCRs) to redirect specificity for protein and carbohydrates antigens. I will reveal how the non-viral Sleeping Beauty (SB) system can be adapted and used to stably express CARs and TCRs to improve the therapeutic potential of clinical grade T cells. These clinical data serve as a foundation for additional genetic engineering to co-express transgenes to improve persistence as well as provide the opportunity for genome editing to eliminate undesired endogenous genes to improve T-cell potency. As genetically modified T cells achieve FDA approval and enter into the mainstream of clinical practice a central question remains how to broaden the number of recipients that can receive such immunotherapy. This anticipated need can met by the use of non-viral gene transfer which provides an avenue for academia and industry to develop distribution systems to widen the human application of next-generation T-cell therapies.
Citation Format: Laurence Cooper. Nonviral gene transfer to redirect T cell specificity. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA47.
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