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.
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.
Authors: Gwendolyn N Y van Gorkom; Roel G J Klein Wolterink; Catharina H M J Van Elssen; Lotte Wieten; Wilfred T V Germeraad; Gerard M J Bos Journal: Antioxidants (Basel) Date: 2018-03-10
Authors: Felician Stancioiu; Georgios Z Papadakis; Stelios Kteniadakis; Boris Nikovaevich Izotov; Michael D Coleman; Demetrios A Spandidos; Aristidis Tsatsakis Journal: Int J Mol Med Date: 2020-06-10 Impact factor: 4.101
Authors: Mohammed Iddir; Alex Brito; Giulia Dingeo; Sofia Sosa Fernandez Del Campo; Hanen Samouda; Michael R La Frano; Torsten Bohn Journal: Nutrients Date: 2020-05-27 Impact factor: 5.717
Authors: Torben K Nielsen; Martin Højgaard; Jon T Andersen; Niklas Rye Jørgensen; Bo Zerahn; Bent Kristensen; Trine Henriksen; Jens Lykkesfeldt; Kári J Mikines; Henrik E Poulsen Journal: Transl Androl Urol Date: 2017-06