Table 2.

Natural killer (NK) cell findings from clinical trials of adoptive cellular transfer for ovarian cancer.

Year	No. of patients	Population	Treatment	Phase	Clinical response	NK cell response	Reference
1989	20 (7 OvCa)	NR	Autologous IP lymphokine-activated killer (LAK) + IL-2	I	2/7 OvCa pts had PR; extended therapy was hampered by IP fibrosis	NR	Urba et al. (165)
1990	24 (10 OvCa)	Recurrent disease	Autologous IP LAK + IL-2	I	2/10 laparoscopic documented PR; 8/10 no response; progressive IP fibrosis	NR	Steis et al. (166)
1990	10	Recurrent disease	Autologous IP LAK + IL-2	I	1/10 (10%) RR; dose-limiting toxicity was ascites accumulation	LAK activity correlated with CD3−CD56+ lymphocytes	Stewart et al. (167)
1991	7	Advanced or recurrent disease	Cyclophosphamide, ACT of tumor-infiltrating lymphocytes (TIL)	II	5/7 (71%) had RR, including 1 (14%) CR	NR	Aoki et al. (197)
	10		Cisplatin, ACT of TIL		9/10 (90%) had RR, including 7 (70%) CR
2011	20 (14 OvCa)	Refractory disease (4+ prior therapies)	Allogeneic IV NK + IL-2	II	Well tolerated overall, but 2 severe adverse events including 1 death; 4/14 (29%) OvCa pts had RR, 8/14 (57%) with SD, and 1/14 (7%) with PD	No sustained in vivo expansion of NK cells was noted	Geller et al. (173)
2014	92	First-line therapy	Primary debulking surgery, carboplatin/paclitaxel ± autologous IV cytokine-induced killer (CIK) cells	III	Progression-free survival: 37.7 vs 22.2 months favor CIK (p = 0.004); overall survival 61.5 vs 55.9 months (NS); well tolerated	NKT (CD3+CD56+) cells increased; NK cells decreased in CIK culture; no changes in peripheral NK cells	Liu et al. (171)
2016	20 (2 OvCa)	Advanced or recurrent disease	Allogeneic IV NK	I	Well tolerated; 1 had SD and 1 had PD	Ex vivo expanded and activated NK cells were generated and safely administered	Yang et al. (174)
2017	1	First-line therapy	Allogeneic IV NK	Case report	PR, with CA-125 decreasing 11,270 to 580 after 6 treatments	Expanded NK cells in culture	Xie et al. (175)