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Umbilical cord blood CD34+ progenitor-derived NK cells efficiently kill ovarian cancer spheroids and intraperitoneal tumors in NOD/SCID/IL2Rgnull mice
| Content Provider | Semantic Scholar |
|---|---|
| Author | Evert, Janneke S. Hoogstad-Van Cany, Jeannette Brand, Dirk Van Den Oudenampsen, Manon Brock, Roland Torensma, Ruurd Bekkers, Ruud L. M. Jansen, Joop Massuger, Leon F. A. G. Dolstra, Harry |
| Copyright Year | 2017 |
| Abstract | Adoptive transfer of allogeneic natural killer (NK) cells is an attractive therapy approach against ovarian carcinoma. Here, we evaluated the potency of highly active NK cells derived from human CD34+ haematopoietic stem and progenitor cells (HSPC) to infiltrate and mediate killing of human ovarian cancer spheroids using an in vivo-like model system and mouse xenograft model. These CD56+Perforin+ HSPC-NK cells were generated under stroma-free conditions in the presence of StemRegenin-1, IL-15, and IL-12, and exerted efficient cytolytic activity and IFNγ production toward ovarian cancer monolayer cultures. Live-imaging confocal microscopy demonstrated that these HSPC-NK cells actively migrate, infiltrate, and mediate tumor cell killing in a three-dimensional multicellular ovarian cancer spheroid. Infiltration of up to 30% of total HSPC-NK cells within 8 h resulted in robust tumor spheroid destruction. Furthermore, intraperitoneal HSPC-NK cell infusions in NOD/SCID-IL2Rγnull (NSG) mice bearing ovarian carcinoma significantly reduced tumor progression. These findings demonstrate that highly functional HSPC-NK cells efficiently destruct ovarian carcinoma spheroids in vitro and kill intraperitoneal ovarian tumors in vivo, providing great promise for effective immunotherapy through intraperitoneal HSPC-NK cell adoptive transfer in ovarian carcinoma patients. |
| File Format | PDF HTM / HTML |
| DOI | 10.1080/2162402X.2017.1320630 |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f6/c8/koni-06-08-1320630.PMC5593716.pdf |
| PubMed reference number | 28919991 |
| Alternate Webpage(s) | https://doi.org/10.1080/2162402X.2017.1320630 |
| Journal | Medline |
| Volume Number | 6 |
| Journal | Oncoimmunology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |