Monjezi R, Miskey C, Gogishvili T, Schleef M, Schmeer M, Einsele H, Ivics Z, Hudecek M (2017)
Publication Type: Journal article
Publication year: 2017
Book Volume: 31
Pages Range: 186-194
Journal Issue: 1
DOI: 10.1038/leu.2016.180
Immunotherapy with T cell modified with gamma-retroviral or lentiviral (LV) vectors to express a chimeric antigen receptor (CAR) has shown remarkable efficacy in clinical trials. However, the potential for insertional mutagenesis and genotoxicity of viral vectors is a safety concern, and their cost and regulatory demands a roadblock for rapid and broad clinical translation. Here, we demonstrate that CAR T cells can be engineered through non-viral Sleeping Beauty (SB) transposition of CAR genes from minimalistic DNA vectors called minicircles (MCs). We analyzed genomic distribution of SB and LV integrations and show that a significantly higher proportion of MC-derived CAR transposons compared with LV integrants had occurred outside of highly expressed and cancer-related genes into genomic safe harbor loci that are not expected to cause mutagenesis or genotoxicity. CD19-CAR T cells engineered with our enhanced SB approach conferred potent reactivity in vitro and eradicated lymphoma in a xenograft model in vivo. Intriguingly, electroporation of SB MCs is substantially more effective and less toxic compared with conventional plasmids, and enables cost-effective rapid preparation of therapeutic CAR T-cell doses. This approach sets a new standard in advanced cellular and gene therapy and will accelerate and increase the availability of CAR T-cell therapy to treat hematologic malignancies.
APA:
Monjezi, R., Miskey, C., Gogishvili, T., Schleef, M., Schmeer, M., Einsele, H.,... Hudecek, M. (2017). Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors. Leukemia, 31(1), 186-194. https://doi.org/10.1038/leu.2016.180
MLA:
Monjezi, R., et al. "Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors." Leukemia 31.1 (2017): 186-194.
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