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Review
. 2013;2013(1):234-46.
doi: 10.1182/asheducation-2013.1.234.

Bringing natural killer cells to the clinic: ex vivo manipulation

Richard W Childs  1 , Maria Berg
Affiliations
Review

Bringing natural killer cells to the clinic: ex vivo manipulation

Richard W Childs et al. Hematology Am Soc Hematol Educ Program. 2013.

Abstract

Recently, there has been a substantial gain in our understanding of the role that natural killer (NK) cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations.

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Conflict of interest statement

Disclosures Conflict-of-interest disclosure: The authors declare no competing financial interests. Off-label drug use: None disclosed.

Figures

Figure 1.
Figure 1.
Methods to activate and/or ex vivo expand human NK cells for infusion in patients with cancer.
Figure 2.
Figure 2.
Phenotype and function of freshly-isolated, IL-2-activated and expanded NK cells. (A) Phenotype of freshly-isolated versus expanded NK cells. (B) Cytotoxicity of NK cells against tumor cells. Used with permission from Berg et al.
Figure 3.
Figure 3.
Fold expansion of ex vivo–expanded clinical grade NK cells and their characteristics on day of infusion. (A) NK cells were adoptively infused into cancer patients on the day of harvest. A total of 78 NK cell cultures expanded using irradiated EBV-LCL feeder cells were infused 14-27 days after culture initiation. (B) Phenotype/purity and viability of 78 clinical-grade NK cell products expanded over 14-27 days from cancer patients using EBV-LCL feeders. Used with permission from Reger et al.
Figure 4.
Figure 4.
Cytotoxicity of human NK cells against tumor cells and persistence in vivo following adoptive transfer in immunodeficient mice. Left: NK cytoxicity versus TRAIL-sensitized kidney cancer cells. Right: NK cell persistence in vivo. NK cells were labeled with DiR near infrared dye and imaged every 6-12 hours after intraperitoneal NK cell infusion into CB.17 SCID-beige mice. IL-2 (100 000 U) was administered intraperitoneally every 12 hours. Used with permission from Berg et al.
Figure 5.
Figure 5.
NK cell trogocytosis as a method to increase NK cell surface expression of CCR7. Used with permission from Somanchi et al.
Figure 6.
Figure 6.
Effects of freeze/thawing on the cytotoxicity and phenotype of expanded NK cells. Used with permission from Berg et al.
See this image and copyright information in PMC

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