The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells

Rettinger, Eva; Kuçi, Selim; Naumann, Ivonne; Becker, P. S. A.; Kreyenberg, Hermann; Anzaghe, Martina; Willasch, André; Koehl, Ulrike; Bug, Gesine; Ruthardt, Martin; Klingebiel, Thomas; Fulda, Simone; Bader, Peter

doi:10.3109/14653249.2011.613931

Cited by 88 publications

(113 citation statements)

References 47 publications

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“…7 Most of the expanded cells showed a CD3 þ CD56 À T-cell phenotype coexpressing TCRa/b. T cells with this phenotype have been associated with GVHD-induction, especially in the haploidentical transplantation setting.…”

Section: Total Number Of Cellsmentioning

confidence: 99%

“…Percentage of total cells 7.5x10 7 5.0x10 7 2. Cytokine-induced killer (CIK) cells represent a heterogeneous population of polyclonal CD3 þ CD56 þ T cells with phenotypic and functional properties of natural killer (NK) cells, which arise from CD3 þ CD56 À CIK cell progenitors.…”

Section: Total Number Of Cellsmentioning

confidence: 99%

“…CIK cell generation described previously 7 was performed under good manufacturing practice (GMP)-conditions. After 10 days of culture, cells were characterized by flow cytometry as previously described, 7 harvested and infused immediately. After infusion, patients received immune monitoring as previously described.…”

Section: Total Number Of Cellsmentioning

confidence: 99%

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Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Rettinger

Bönig

Wehner

et al. 2013

Bone Marrow Transplant

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Haploidentical hematopoietic SCT is an established treatment for high-risk leukemia in patients lacking a HLA-identical donor, and is also being evaluated for refractory solid tumors.The therapeutic success of any SCT for malignant disease is limited by relapse. Impending relapse can be treated by DLI, but DLI is of limited value when initiated during overt relapse. 1 Moreover, the high T-cell doses required for DLI pose a risk of severe GVHD, specifically in the haploidentical setting.

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Section: Total Number Of Cellsmentioning

confidence: 99%

Section: Total Number Of Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Rettinger

Bönig

Wehner

et al. 2013

Bone Marrow Transplant

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“…Rettinger et al (7) and Meng et al (8) demonstrated that IL-15 and IL-21, respectively were able to promote the proliferative, and cytotoxic activity of cytokine-induced killer cells (CIKs). Rutella et al (9) noted that thymoglobulin efficiently expanded the CIK population, and that the CIKs generated by thymoglobulin were feasible and safe for solid tumor treatment.…”

Section: Introductionmentioning

confidence: 99%

Identification of a protein associated with the activity of cytokine‑induced killer cells

et al. 2017

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Abstract. Cytokine-induced killer cells (CIKs) adoptive immunotherapy for efficient antitumor ability is used clinically, but details regarding the proteins associated with CIK activity remain unclear. In the current study, the cytotoxicity of CIKs on hepatoma was identified to be significantly downregulated by 1.61-fold following gentamincin treatment. Further research revealed that a differentially expressed protein (P43) was significantly downregulated by 1.22-fold using one-dimensional gel electrophoresis analysis. Of these, the P43 was identified as human haptoglobin using liquid chromatography-mass spectrometry. Western blotting demonstrated that the haptoglobin specifically reacted with rabbit anti-human-haptoglobin. Furthermore, western blotting results verified that the haptoglobin was significantly downregulated by 1.17-fold compared with the control group. In addition, the expression of haptoglobin mRNA was significantly downregulated by 1.73-fold following gentamincin treatment. Taken together, the results of the present study demonstrated that the expression of haptoglobin protein was associated with the activity of CIKs, and the results will be beneficial to the further investigation of CIK activity-enhancement mechanism.

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“…From a cost-effectiveness standpoint, the group 3 protocol would be more appropriate because of the lower IL-2 concentration used; however, group 4 has the advantage of generating effective CIK cells in a shorter 14-day time period. Recently, researchers have expanded upon classical protocols to attempt to improve CIK cell proliferation and efficacy with additional cytokine inducers such as IL-6, IL-7, IL-15, IL-21, thymoglobulin, or co-culture with dendritic cells (Bonanno et al, 2010;Heninger et al, 2012;Lin et al, 2012;Rettinger et al, 2012;Schmidt et al, 2004;Zhao et al, 2012). More research, including further delineation of CIK cell characteristics, is needed to see if different combinations of these innovative inducers with those outlined in experimental groups 3 and 4 in this study could generate even higher percentages of CD3 + CD56 + CIK cells.…”

mentioning

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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The cytotoxic potential of interleukin-15-stimulated cytokine-induced killer cells against leukemia cells

Cited by 88 publications

References 47 publications

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Feasibility of IL-15-activated cytokine-induced killer cell infusions after haploidentical stem cell transplantation

Identification of a protein associated with the activity of cytokine‑induced killer cells

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

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