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

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

doi:10.1016/j.jcyt.2015.01.004

Cited by 74 publications

(63 citation statements)

References 30 publications

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“…This phenomenon was reported in a previous study demonstrating that PBMCs derived from healthy donors had a high proportion of NK cells and a relatively low proportion of CD3 + T cell following the in vitro expansion; however, no other subgroup analysis was performed (31). It was reported that the number of harvested NK cells in the culture was associated with the number of NK cells in the peripheral blood sample originally drawn (48).…”

Section: Discussionmentioning

confidence: 70%

“…This effect may be similar to the role of feeder cells. OKT3 has been commonly used in PBMCs to induce the proliferation of NK cells, suggesting that OKT3 does not only induce T-cell proliferation but also promotes T-cell generating cytokines that support NK cell proliferation (31). However, in the present study, OKT3 co-stimulation evidently enhanced the expansion of the total cells, but primarily induced PBMCs to differentiate into CD3 + T cells, as the proportion of CD3 + CD8 + and CD3 + CD4 + T cells was higher in the HER-2 and anti-CD3 antibody co-stimulation system.…”

Section: Discussionmentioning

confidence: 99%

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Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

Chen

et al. 2017

Exp Ther Med

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Abstract. Cell-based adoptive immunotherapy for the treatment of various cancer types has attracted the attention of scientists. However, due to the absence of unitary standard protocols to produce large quantities of clinical-grade effector cells, it remains challenging to translate the experimental findings into clinical applications. The present study used methods complying with good manufacturing practice to induce effector cells from human peripheral blood mononuclear cells (PBMCs) of healthy donors by interleukin-2 and anti-Her-2 antibody with or without anti-CD3 antibodies (OKT3). The results indicated that the addition of OKT3 resulted in a greater expansion of the total cells and CD8 + T cells, and primarily induced the PBMCs to differentiate into CD3 + T cells. Regardless of the presence of OKT3, the expression of activating receptor of natural killer (NK) group 2, member D, and the inhibitory receptors of CD158a and CD158b on NK cells and NKT cells was increased, while the expression of NKp46 was inhibited on NK cells, but not on NKT cells. Furthermore, OKT3 did not affect the toxicity of the effector cells. Subgroup analysis indicated that although a variation of the composition of effector cells was present in different individuals under identical culture conditions, consistent marker expression on effector cells and target cell-killing effects were observed in different subgroups treated with or without OKT3. Furthermore, western blot analysis indicated that OKT3, apart from its involvement in cell cycle regulation, affects transcription and protein translation during processes of proliferation and differentiation. The present study provided experimental data regarding the production of effector cells for adoptive immunotherapy as a clinical application.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

Chen

et al. 2017

Exp Ther Med

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“…According to them, these cells have the ability to "kill" tumor cells without the need for sensitization of direction, and that ascorbic acid promotes their proliferation. 24 conclusion Studies have reported the use of ascorbic acid in the prevention and treatment of cancer. However, there is controversy about its antioxidant and antitumor role.…”

Section: Resultsmentioning

confidence: 96%

Ascorbic acid in the prevention and treatment of cancer

Mata

Carvalho

Alencar

et al. 2016

Rev. Assoc. Med. Bras.

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Mata aMOF da et al. 680rev assoC med bras 2016; 62(7):680-686 This review is aimed at the systematic mapping of ascorbic acid in the prevention and/or treatment of cancer in clinical and non-clinical studies from 2011 to 2015, in order to understand dose-response variations as well as its mechanisms of action as an antioxidant and antitumor agent. Seventy-eight articles were retrieved from the PubMed/Bireme database, of which only 30 included ascorbic acid in the prevention and/or treatment of cancer. However, there are controversies regarding doses and a lack of clinical studies featuring its mechanism of action more clearly. Other studies are needed to understand dose-response variations, as well as its targeting mechanisms of action, both as an antioxidant and antitumor agent, to assist treatment and prevention of cancer, aiming at better quality of life for both patients and the general population.

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“…Immunotherapy may improve OS without generating a significant PSA response. AA may enhance immune-cell activity (31), but no study has shown any cancer-directed immunotherapy using AA alone. To pursue possible effects of AA not related to PSA expression by tumor cells, additional biomarkers of the PCWG-2 and two prognostic nomograms were included (10,17,18).…”

Section: Discussionmentioning

confidence: 99%

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial

Nielsen

Højgaard

Andersen

et al. 2017

Transl. Androl. Urol.

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BackgroundAscorbic acid (AA) has in vivo cytotoxic properties at concentrations that can only be achieved through intravenous (IV) administration in humans. Treatment with intravenous AA is widely and increasingly used in complementary medicine despite a lack of clinical evidence for the efficacy of this treatment.MethodsThis non-comparative, single-center, phase II trial included patients with chemotherapy-naïve, metastatic castration-resistant prostate cancer (mCRPC) from an outpatient clinic to evaluate the efficacy and safety of IV AA therapy. Patients received weekly infusions of AA (week 1, 5 g; week 2, 30 g; and weeks 3–12, 60 g) followed by efficacy evaluation at 12 weeks. The primary endpoint for efficacy was a 50% reduction in the prostate-specific antigen (PSA) level. The secondary endpoints included changes in health-related quality of life (HRQoL), biomarkers of bone metabolism, inflammation and bone scans. Clinicaltrials.gov identifier: NCT01080352.ResultsTwenty-three patients were enrolled in this study, and 20 completed the efficacy evaluation at 12 weeks. The mean baseline PSA level was 43 µg/L. No patient achieved a 50% PSA reduction; instead, a median increase in PSA of 17 µg/L was recorded at week 12. Among the secondary endpoints, no signs of disease remission were observed. In total, 53 adverse events (AEs) were recorded. Eleven were graded as “serious”. Three AEs were directly related to AA, and all of which were related to fluid load.ConclusionsInfusion with 60 g of AA did not result in disease remission. This study does not support the use of intravenous AA outside clinical trials.

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

Cited by 74 publications

References 30 publications

Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

Large scale ex vivo expansion of clinical‑grade effector cells for adoptive immunotherapy

Ascorbic acid in the prevention and treatment of cancer

Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: a single-arm phase II trial

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