Acute Myeloid Leukemia Treatment Specificity Enhanced With Stem Cell Editing

In Nature, researchers at Boston Children's Hospital, Dana-Farber Cancer Institute, and elsewhere outline a strategy for more precisely targeting acute myeloid leukemia with immunotherapy. With the help of optimized CRISPR-Cas9 editing of donor CD34-positive hematopoietic stem/progenitor cells (HSPCs), the team tweaked immunotherapy-targeted epitopes that are also present in normal blood progenitor or immune cells, including the FLT3, KIT, and IL-3 receptor genes, to prevent targeting of engrafted HSPCs during AML treatment. "Here we show that epitope engineering of donor HSPCs used for bone marrow transplantation endows hematopoietic lineages with selective resistance to chimeric antigen receptor (CAR) T cells or monoclonal antibodies, without affecting protein function or regulation," the authors write, noting that the approach "enables the targeting of genes that are essential for leukemia survival regardless of shared expression of HSPCs, reducing the risk of tumor immune escape."