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.
Department of Medicine (Division of Hematology, Oncology, and Transplant), University of Minnesota, Minneapolis, Minnesota, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
David L
DL
Hermanson
Department of Medicine (Division of Hematology, Oncology, and Transplant), University of Minnesota, Minneapolis, Minnesota, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Laura
L
Bendzick
Department of Obstetrics, Gynecology, and Women's Health (Division of Gynecologic Oncology), University of Minnesota, Minneapolis, Minnesota, USA.
Lee
L
Pribyl
Department of Medicine (Division of Hematology, Oncology, and Transplant), University of Minnesota, Minneapolis, Minnesota, USA.
Valarie
V
McCullar
Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Rachel Isaksson
RI
Vogel
Department of Medicine (Division of Hematology, Oncology, and Transplant), University of Minnesota, Minneapolis, Minnesota, USA.
Jeff S
JS
Miller
Department of Obstetrics, Gynecology, and Women's Health (Division of Gynecologic Oncology), University of Minnesota, Minneapolis, Minnesota, USA.
Melissa A
MA
Geller
Department of Medicine (Division of Hematology, Oncology, and Transplant), University of Minnesota, Minneapolis, Minnesota, USA.|Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, USA.
Dan S
DS
Kaufman
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007694:Killer Cells, Natural / Q000166:cytology*; D051379:Mice; D010051:Ovarian Neoplasms / Q000097:blood / Q000628:therapy*
Immunotherapy; Induced pluripotent stem cells; Natural killer cells; Ovarian cancer