Targeting CD45 by gene-edited CAR T cells for leukemia eradication and hematopoietic stem cell transplantation preconditioning.

ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells. Here, we introduce a preconditioning strategy targeting CD45 on hematopoietic cells with CAR45 T cells. To avoid fratricide of CD45 CAR T cells, genomic disruption of the CD45 gene was performed on human CD45 CAR T cells in combination with the signaling kinase inhibitor

SUBMITTER: Stepanova VM 

PROVIDER: S-EPMC11735918 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature