Genetic Manipulation of Natural Killer Cells to Express c-MPL Growth Factor Receptor as a Therapy for Cancer

This technology includes genetic manipulation of natural killer (NK) cells to express thrombopoietin receptor (c-MPL) growth factor receptor as strategy to augment NK cell proliferation and anti-tumor immunity. Many investigational adoptive immunotherapy regimens utilizing NK cells require the administration of IL-2 or IL-15 cytokines to support the survival and function of the cells in patients, however administration of these cytokines causes a number of serious dose-dependent toxicities. In the presence of thrombopoietin (TPO) ligand, lentiviral transduction of primary human NK cells to express c-MPL enhanced in vitro cellular proliferation and increased degranulation and cytokine production towards target cells. Data from our study could be translated to a clinical trial setting, where the infusion of genetically modified c-MPL-expressing NK cells is followed by the off-label administration of an FDA-approved TPO-mimetic (e.g., eltrombopag, romiplostim).