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- W2561272008 abstract "Chimeric antigen receptor (CAR)-redirected T-cells have given rise to long-term durable remissions and remarkable objective response rates in patients with refractory leukemia. At present, CAR technology is administered through the custom-made manufacturing of therapeutic products from each patient's own T-cells. However, this patient-specific autologous paradigm is a significant limiting factor in the large-scale deployment of CAR technology. We have developed a platform for the production of “off-the-shelf” CAR T-cells from unrelated third-party donor T-cells. This platform utilizes Transcription Activator-Like Effector Nuclease (TALEN) gene editing technology to inactivate the TCRα constant (TRAC) gene, eliminating the potential for T-cells bearing alloreactive TCR's to mediate Graft versus Host Disease (GvHD). We have previously demonstrated that editing of the TRAC gene can be achieved at high frequencies, obtaining up to 80% of TCRα negative cells. This allows us to efficiently produce TCR-deficient T-cells that have been shown to no longer mediate alloreactivity in a xeno-GvHD mouse model. Acute myeloid leukemia (AML) is incurable in the majority of patients. While allogeneic stem cell transplantation remains the most effective therapy for AML to date, other types of cellular therapy have not yet been successful in this disease. We have adapted this allogeneic platform to the production of T cells targeting CD123, the alpha chain of the interleukin-3 receptor, which is expressed in tumor cells of patients with AML. We will present both in vitro and in vivo data demonstrating specific anti-tumor activity of engineered CAR T cells against AML cells. The ability to carry out large scale manufacturing of allogeneic, non alloreactive CD123 specific T cells from a single healthy donor will offer the possibility of an off-the-shelf treatment that would be immediately available for administration to a large number of AML patients." @default.
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- W2561272008 date "2016-05-01" @default.
- W2561272008 modified "2023-10-17" @default.
- W2561272008 title "397. Allogenic CAR T-Cells Targeting CD123 Effectively Eliminate Myeloid Leukemia Cells" @default.
- W2561272008 doi "https://doi.org/10.1016/s1525-0016(16)33206-3" @default.
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