IL-15 overexpression promotes memory program and anti-tumor activity of CD64 CAR T cells in a preclinical AML model.

ABSTRACT: The prognosis of relapsed or refractory acute myeloid leukemia (r/r AML) patients remains poor due to lack of novel therapies. We previous demonstrated that chimeric antigen receptor (CAR) T cells targeting CD64 have the potential to treat AML with minimal toxicity to hematopoietic stem/progenitor cells. However, the efficacy was limited in AML mouse models. Interleukin-15 (IL-15), a cytokine that promotes T cell survival and proliferation, has been shown to enhance CAR T cell activity. Here, we engineer CD64 CAR T cells with overexpression of IL-15 and evaluate the function. IL-15-armed CAR T cells exhibit enhanced cytolytic activity against AML cells, improve expansion and persistence in vitro, and favor a memory phenotype while reducing exhaustion and apoptosis. In mouse model, IL-15-ar

SUBMITTER: Shan L 

PROVIDER: S-EPMC12909298 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature