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Abstract Title:

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

Abstract Source:

Cytotherapy. 2015 May ;17(5):613-20. Epub 2015 Mar 5. PMID: 25747742

Abstract Author(s):

Mirelle J A J Huijskens, Mateusz Walczak, Subhashis Sarkar, Florance Atrafi, Birgit L M G Senden-Gijsbers, Marcel G J Tilanus, Gerard M J Bos, Lotte Wieten, Wilfred T V Germeraad

Article Affiliation:

Mirelle J A J Huijskens

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.

Study Type : In Vitro Study

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