Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody

Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modi...

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Bibliographic Details
Published in:Scientific reports 2017-09, Vol.7 (1), p.11075-13, Article 11075
Main Authors: Lee, Hong-Rae, Son, Cheol-Hun, Koh, Eun-Kyoung, Bae, Jae-Ho, Kang, Chi-Dug, Yang, Kwangmo, Park, You-Soo
Format: Article
Language:English
Subjects:
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Antitumor activity
Cancer
CD16 antigen
Cell activation
Cell culture
Cell proliferation
Contamination
Cytotoxicity
Humanities and Social Sciences
Irradiation
Leukocytes (mononuclear)
Lymphocyte receptors
Lymphocytes T
Monoclonal antibodies
multidisciplinary
Natural killer cells
NKG2 antigen
Peripheral blood mononuclear cells
Science
Science (multidisciplinary)
T cell receptors
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Summary:Natural killer (NK) cells are considered a promising strategy for cancer treatment. Various methods for large-scale NK cell expansion have been developed, but they should guarantee that no viable cells are mixed with the expanded NK cells because most methods involve cancer cells or genetically modified cells as feeder cells. We used an anti-CD16 monoclonal antibody (mAb) and irradiated autologous peripheral blood mononuclear cells (PBMCs) (IrAPs) to provide a suitable environment (activating receptor-ligand interactions) for the NK cell expansion. This method more potently expanded NK cells, and the final product was composed of highly purified NK cells with lesser T-cell contamination. The expanded NK cells showed greater upregulation of various activation receptors, CD107a, and secreted larger amounts of interferon gamma. IrAPs expressed NKG2D ligands and CD48, and coengagement of CD16 with NKG2D and 2B4 caused potent NK cell activation and proliferation. The expanded NK cells were cytotoxic toward various cancer cells in vitro and in vivo . Moreover, irradiation or a chemotherapeutic drug further enhanced this antitumor effect. Therefore, we developed an effective in vitro culture method for large-scale expansion of highly purified cytotoxic NK cells with potent antitumor activity using IrAPs instead of cancer cell-based feeder cells.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-09259-1