Transforming growth factor beta-resistant natural killer cells
AssigneeResearch Institute At Nationwide Children's Hospital
InventorsDean Anthony Lee, Jennifer Ann Foltz-Stringfellow, Jena Edwards-Moseman
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Abstract
An NK cell with low SMAD3 expression and altered gene expression profile resulting in high cytokine expression and TGF-β superfamily resistance is described, refered to herein as TGF-β superfamily-imprinted Natural Killer Cells (TGFβi NK cells). A method of treating cancer or infection in a subject in need thereof is described. The method includes administering a therapeutically effective number of TGFβi NK cells to the subject. A method of producing TGFβi NK cells is described by in vitro activation of natural killer cells in the presence of a TGF-β superfamily cytokine.
Claims15
A method of making transforming growth factor-beta imprinted natural killer cells (TGF-βi NK), comprising activating and expanding natural killer cells in vitro by culturing the natural killer cells for at least 14 days in the presence of one of feeder cells, exosomes, or nanoparticles that express membrane bound interleukin-21 (IL-21) or membrane bound interleukin-15 (IL-15) and in the presence of an amount of TGF-β sufficient to render the natural killer cells resistant to TGF-β, wherein the resulting natural killer cells are TGF-βi NK cells that maintain cytotoxicity relative to control NK cells cultured without the presence of TGF-β.
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