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2017 ; 6
(8
): e1320630
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Umbilical cord blood CD34(+) progenitor-derived NK cells efficiently kill ovarian
cancer spheroids and intraperitoneal tumors in NOD/SCID/IL2Rg(null) mice
#MMPMID28919991
Hoogstad-van Evert JS
; Cany J
; van den Brand D
; Oudenampsen M
; Brock R
; Torensma R
; Bekkers RL
; Jansen JH
; Massuger LF
; Dolstra H
Oncoimmunology
2017[]; 6
(8
): e1320630
PMID28919991
show ga
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 IFN? 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-IL2R?(null) (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.