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Cytotherapy. 2015 May;17(5):613-20. doi: 10.1016/j.jcyt.2015.01.004. Epub 2015 Mar 5.

Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy.

Author information

1
Department of Internal Medicine, Division of Haematology, Maastricht University Medical Center, Maastricht, The Netherlands.
2
Department of Transplantation Immunology, Maastricht University Medical Center, Maastricht, The Netherlands.
3
Department of Internal Medicine, Division of Haematology, Maastricht University Medical Center, Maastricht, The Netherlands. Electronic address: w.germeraad@maastrichtuniversity.nl.

Abstract

BACKGROUND AIMS:

Natural killer (NK) cell-based immunotherapy is a promising treatment for a variety of malignancies. However, generating sufficient cell numbers for therapy remains a challenge. To achieve this, optimization of protocols is required.

METHODS:

Mature NK cells were expanded from peripheral blood mononuclear cells PBMCs in the presence of anti-CD3 monoclonal antibody and interleukin-2. Additionally, NK-cell progenitors were generated from CD34(+) hematopoietic stem cells or different T/NK-cell progenitor populations. Generated NK cells were extensively phenotyped, and functionality was determined by means of cytotoxicity assay.

RESULTS:

Addition of ascorbic acid (AA) resulted in more proliferation of NK cells without influencing NK-cell functionality. In more detail, PBMC-derived NK cells expanded 2362-fold (median, range: 90-31,351) in the presence of AA and were capable of killing tumor cells under normoxia and hypoxia. Moreover, hematopoietic stem cell-derived progenitors appeared to mature faster in the presence of AA, which was also observed in the NK-cell differentiation from early T/NK-cell progenitors.

CONCLUSIONS:

Mature NK cells proliferate faster in the presence of phospho-L-AA, resulting in higher cell numbers with accurate functional capacity, which is required for adoptive immunotherapy.

KEYWORDS:

NK cell; ascorbic acid; cancer; cellular immunotherapy; hematopoietic stem cell

PMID:
25747742
DOI:
10.1016/j.jcyt.2015.01.004
[Indexed for MEDLINE]

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