Targeting CD117 on hematopoietic stem and progenitor cells impairs CAR T cell activity.

ABSTRACT: CD117 is a cell-surface receptor expressed on hematopoietic stem and progenitor cells and acute myeloid leukemia (AML), and thus CD117-targeting chimeric antigen receptor T cells (CART117) can function as both conditioning for hematopoietic stem cell transplantation and a therapy for AML. We developed human and mouse CART117 to evaluate the safety and feasibility of targeting CD117 in preclinical mouse models. Human CART117 had potent anti-tumor activity while also mediating significant hematopoietic toxicity in a humanized mouse model. Murine CART117 (mCART117) led to systemic and hematopoietic toxicity without anti-leukemic benefit in immunocompetent C57BL/6 mice. Intriguingly, mCART117 was able to eliminate CD117⁺ cells in the spleen but not in the bone marrow (BM). Of note,

SUBMITTER: Thomas R 

PROVIDER: S-EPMC12432900 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature