Faculty, Staff and Student Publications
Publication Date
1-1-2025
Journal
Journal of Cellular and Molecular Medicine
Abstract
Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines and primary AML cells. We observed that FT538 iPSC-NKs induce effector-to-target cell ratio dependent apoptosis in cell lines and primary AML cells, including cells from high-risk patients. Flow cytometric analysis revealed that FT538 iPSC-NKs induce AML cell death when combined with the AML therapies: cytarabine, venetoclax and gilteritinib. Moreover, cytarabine did not affect FT538 iPSC-NK viability, suggesting that iPSC-derived NK therapies and chemotherapy may be a promising treatment combination. This study provides the basis for further study of iPSC-derived NK cell therapies as a treatment option for high-risk AML patients, particularly those with disease resistant to standard therapies.
Keywords
Humans, Killer Cells, Natural, Leukemia, Myeloid, Acute, Induced Pluripotent Stem Cells, Apoptosis, Cytarabine, Cell Line, Tumor, Sulfonamides, Bridged Bicyclo Compounds, Heterocyclic
DOI
10.1111/jcmm.70169
PMID
39797701
PMCID
PMC11724334
PubMedCentral® Posted Date
1-11-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Medical Sciences Commons, Oncology Commons