Induced Pluripotent Stem Cell-Derived Natural Killer Cells for Treatment of Ovarian Cancer

David L. Hermanson, Laura Bendzick, Lee Pribyl, Valarie J Mc Cullar, Rachel I Vogel, Jeffrey S Miller, Melissa A Geller, Dan S. Kaufman

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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. Stem Cells 2016;34:93-101

Original languageEnglish (US)
Pages (from-to)93-101
Number of pages9
JournalSTEM CELLS
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
This research was supported by funding from the Minnesota Ovarian Cancer Alliance (MOCA) (Geller, M) "NK Cell Immunotherapy for Ovarian Cancer", Mayo Clinic Ovarian Cancer SPORE (P50 CA136393), and NIH grant P30 CA77598 using the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. Melissa Geller, MD and Dan Kaufman, MD, PhD are supported by a Research Scholar Grant, RSG-14-151-01-CCE from the American Cancer Society. Dan Kaufman, MD, PhD has support from the Minnesota Ovarian Cancer Alliance and a Minnesota Partnership Grant for Biotechnology. David Hermanson, PhD has been supported by an NIH Hematology Research Training Grant (2T32HL007062) and an Irvington Postdoctoral Fellowship from the Cancer Research Institute.

Keywords

  • Immunotherapy
  • Induced pluripotent stem cells
  • Natural killer cells
  • Ovarian cancer

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