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DKO CD45CAR T-cells are an experimental, allogeneic 'off-the-shelf' CAR-T cell therapy designed to target CD45 (PTPRC), a pan-hematopoietic antigen uniformly expressed on leukemic stem cells in acute myeloid leukemia (AML). Developed by researchers at University College London and the University of Birmingham, these T-cells are engineered using CRISPR/Cas9 to knockout both the endogenous CD45 (PTPRC) gene to prevent CAR-mediated fratricide and the T-cell receptor (TRAC) gene to prevent graft-versus-host disease (GVHD). The therapy utilizes a second-generation CAR construct derived from the YTH24.5 antibody clone with a CD28 costimulatory domain. Additionally, the cells incorporate an inducible Caspase 9 (iCaspase9) suicide gene system, allowing for rapid depletion of the CAR-T cells with rimiducid prior to a subsequent hematopoietic stem cell transplant (SCT) to avoid targeting the donor-derived hematopoietic system.
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