Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer.
Natural killer (NK) cells can provide effective immunotherapy for ovarian cancer. Here, we evaluated the ability of NK cells isolated from peripheral blood (PB) and NK cells derived from induced pluripotent stem cell (iPSC) to mediate killing of ovarian cancer cells in a mouse xenograft model. A mouse xenograft model was used to evaluate the intraperitoneal delivery of three different NK cell populations: iPSC-derived NK cells, PB-NK cells that had been activated and expanded in long-term culture, and overnight activated PB-NK cells that were isolated through CD3/CD19 depletion of PB B and T cells. Bioluminescent imaging was used to monitor tumor burden of luciferase expressing tumor lines. Tumors were allowed to establish prior to administering NK cells via intraperitoneal injection. These studies demonstrate a single dose of any of the three NK cell populations significantly reduced tumor burden. When mice were given three doses of either iPSC-NK cells or expanded PB-NK cells, the median survival improved from 73 days in mice untreated to 98 and 97 days for treated mice, respectively. From these studies, we conclude iPSC-derived NK cells mediate antiovarian cancer killing at least as well as PB-NK cells, making these cells a viable resource for immunotherapy for ovarian cancer. Due to their ability to be easily differentiated into NK cells and their long-term expansion potential, iPSCs can be used to produce large numbers of well-defined NK cells that can be banked and used to treat a large number of patients including treatment with multiple doses if necessary.
['Hermanson|David L|DL|', 'Bendzick|Laura|L|', 'Pribyl|Lee|L|', 'McCullar|Valarie|V|', 'Vogel|Rachel Isaksson|RI|', 'Miller|Jeff S|JS|', 'Geller|Melissa A|MA|', 'Kaufman|Dan S|DS|']
D000818:Animals D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D005434:Flow Cytometry D006801:Humans D007167:Immunotherapy D057026:Induced Pluripotent Stem Cells D007694:Killer Cells, Natural D051379:Mice D010051:Ovarian Neoplasms
Natural killer cells Ovarian cancer Immunotherapy Induced pluripotent stem cells