Cytokine induced killer cell immunotherapy in cancer treatment: from bench to bedside

Arafar, Arashar

doi:10.7603/s40730-014-0012-7

Cited by 6 publications

(5 citation statements)

References 36 publications

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“…Generally, anti-angiogenic effects are modulated through multiple pathways. The key signalling pathway that modulates proliferation of endothelial cells is the vascular endothelium growth (50)(51)(52)(53)(54). In this study, CIK cells were generated by culturing peripheral blood monocytes isolated from healthy donors with interferon-gamma (IFN-) and interleukin-2.…”

Section: Anti-cancermentioning

confidence: 99%

Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms

Chan

Tan

et al. 2020

Chemico-Biological Interactions

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Anti-cancermentioning

confidence: 99%

Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms

Chan

Tan

et al. 2020

Chemico-Biological Interactions

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“…The obtained CIK cells are heterogeneous lymphocytes, in which over 90% are CD3 + cells, and can be divided into two main subsets: CD3 + CD56 + cells and CD3 + CD56 ‐ T cells . Due to the limited initial number, CIK cells need to be expanded ex vivo up to 10 10 cells per infusion to meet the clinical requirements . Moreover, it was reported that the clinical response was related to injected cell numbers; therefore, it is necessary to optimize the ex vivo CIK cells expansion process for better clinical efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…9 The obtained CIK cells are heterogeneous lymphocytes, in which over 90% are CD3 + cells, and can be divided into two main subsets: CD3 + CD56 + cells and CD3 + CD56 -T cells. [14][15][16] Moreover, it was reported that the clinical response was related to injected cell numbers [17][18][19] ; therefore, it is necessary to optimize the ex vivo CIK cells expansion process for better clinical efficacy. [14][15][16] Moreover, it was reported that the clinical response was related to injected cell numbers [17][18][19] ; therefore, it is necessary to optimize the ex vivo CIK cells expansion process for better clinical efficacy.…”

mentioning

confidence: 99%

“…[10][11][12][13] Due to the limited initial number, CIK cells need to be expanded ex vivo up to 10 10 cells per infusion to meet the clinical requirements. [14][15][16] Moreover, it was reported that the clinical response was related to injected cell numbers [17][18][19] ; therefore, it is necessary to optimize the ex vivo CIK cells expansion process for better clinical efficacy.…”

mentioning

confidence: 99%

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Enhanced metabolic activities for ATP production and elevated metabolic flux via pentose phosphate pathway contribute for better CIK cells expansion

2019

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Objective Ex vivo expansion is an effective way to produce cytokine‐induced killer (CIK) cells needed for clinical trials. Here, ex vivo expansion and metabolism characters of CIK cells in static and dynamic cultures and the relationship between cell expansion and metabolism were investigated. Materials and methods Oxygen transfer efficiency was assessed by computational fluid dynamics technique. Cell phenotype, apoptosis and of transporter expression were determined by flow cytometry and Western blotting. Metabolites and enzyme activities were assessed by biochemical methods. Results Dynamic cultures favoured better CIK cell expansion without impairing their phenotype and cytotoxicity, enhanced oxygen transfer efficiency. The glucose metabolism flux of cells in dynamic cultures was enhanced by upregulating surface glucose transporter 1 expression and phosphofructokinase activity. Moreover, pentose phosphate pathway (PPP) metabolic flux was enhanced through upregulating glucose‐6‐phosphate dehydrogenase activity. Glutaminolysis was also accelerated via boosting glutamine transporters expression, glutaminase (GLS) and glutamate dehydrogenase activities. Together with higher oxygen consumption rate and extracellular acidification rate, it was suggested that cells in dynamic cultures were in a more vigorous metabolic state for ATP production. Conclusion Dynamic cultures accelerated glucose and glutamine metabolic flux to promote ATP production, elevated glucose metabolic flux through PPP to promote biosynthesis for better cell expansion. These findings may provide the basis for ex vivo CIK cell expansion process optimization.

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“…The qualifier "cytokine-induced killer" indicates that they are generated via administration of cytokines during in vitro culture (Arafar, 2014;Linn and Hui, 2010). Cells which have the most potential effector function in CIK culture coexpress CD3 and CD56 surface molecules; possess a potent, MHC-unrestricted tumor-killing ability; and significantly reduced alloreactivity (Sangiolo et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Culture and differentiation of cytokine-induced killer cells from umbilical cord blood-derived mononuclear cells

Duong

et al. 2016

Biomed Res Ther

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Abstract-Cytokine-induced killer cells (CIK) are cytotoxic T cells, which have both NK and T cell properties. These cells are characterized by potent, non-MHC-restricted cytotoxicity and reduced alloreactivity, which make them appealing for use in adoptive immunotherapy of cancer and virus infections. In this study, CIK cells were generated by stimulating umbilical cord blood-derived mononuclear cells (UCB-MNCs) with interferon-gamma (IFN-) on day 0. Anti-CD3 antibody and interleukin-2 (IL-2) were added after 24 hours at four different experimental concentration combinations in order to identify the optimal cytokine amounts for CIK cell proliferation. Cells were collected at four time points over a 21-day period (day 0, 7, 14, 21) for analysis of cell marker presentation using flow cytometry, as well as transcription-level cytokine production using RT-PCR. The results showed that in the 21-day culture, the average final expansion levels of CD3 + CD56 + CIK cell were in the range of hundredfold, accounted for 26% in the bulk culture. Most important, these cells strongly expressed granzyme B (80.87%), a potent factor involved in cell-mediated cytotoxicity. These CIK cells also transcriptionally overexpressed the three cytokine genes that produce IFN-, tumor necrosis factor-alpha (TNF-), and IL-2; these are key for immune cell mobilization against tumors as well as foreign pathogens. Our research establishes an effective cytokine concentration and time protocol for use in generation of CIK cells from UCB-MNCs, potentiating greater applications of CIK cell-adoptive immunotherapy in both research and clinical settings. Thus, the 3 rd and 4 th experimental conditions both stimulated CIK cell differentiation with 50 ng/ml of anti-CD3 antibody, but with IL-2 concentrations of 500 U/ml and 1000 U/ml, respectively.

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Cytokine induced killer cell immunotherapy in cancer treatment: from bench to bedside

Cited by 6 publications

References 36 publications

Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms

Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms

Enhanced metabolic activities for ATP production and elevated metabolic flux via pentose phosphate pathway contribute for better CIK cells expansion

Culture and differentiation of cytokine-induced killer cells from umbilical cord blood-derived mononuclear cells

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