Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells

Wang, Peng; Yu, Jin; Gao, Song; An, Xiu Mei; Ren, Xiu Bao; Wang, Xiao Guang; Li, Wen liang

doi:10.1016/j.cellimm.2008.04.014

Cited by 21 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specific cytotoxicity was calculated as in previous studies (14). 5 , 1x10 6 or 1x10 7 , in 100 μl HBSS) were injected intravenously into animals bearing U-87MG tumor in their brains once a week for four weeks (Fig. 4A).…”

Section: Generation Of Human and Mouse Cik Cellsmentioning

confidence: 99%

“…Two previous studies showed that CIK cells have significant therapeutic effects against GBM in vivo (7,8). However, intracranial CIK cell injection method (7) and results from subcutaneous GBM xenograft animal model (8) are difficult to translate immediately into the clinical settings.…”

Section: Introductionmentioning

confidence: 99%

“…Various immune cell types such as dendritic cells, lymphokine-activated killer (LAK) cells, natural killer (NK) cells, cytotoxic T cells and cytokineinduced killer (CIK) cells have been studied as a potential candidate for effective immunotherapy (4)(5)(6)(7)(8). Among them, CIK cells, characterized by the co-expression of CD3 and CD56 molecules, demonstrated potent cytolytic activity in a MHC-unrestricted manner (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…However, intracranial CIK cell injection method (7) and results from subcutaneous GBM xenograft animal model (8) are difficult to translate immediately into the clinical settings. Combinational effects with temozolomide (TMZ) also need to be considered since it is the most widely-used chemotherapeutic agent against GBM in the clinic.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma

Jin

Joo²,

Lee³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. The presence of active immunity within the brain supports the possibility of effective immunotherapy for glioblastoma (GBM). To provide a clinically-relevant adoptive immunotherapy for GBM using ex vivo expanded cytokineinduced killer (CIK) cells, the treatment capability of CIK cells, either alone or in combination with temozolomide (TMZ) were evaluated. Human CIK (hCIK) cells were cultured from PBMC using activating anti-CD3 antibody and IL-2, which were 99% CD3 + , 91% CD3 + CD8 + and 29% CD3 + CD56 + . In vitro, hCIK cells showed tumor-specific cytotoxicity against U-87MG human GBM cells. When hCIK cells were injected into tail veins of immune-compromised mice bearing U-87MG tumors in their brains, numerous CIK cells infiltrated into the brain tumors. CIK treatments (1x10 5 , 1x10 6 or 1x10 7 , once a week for four weeks) inhibited the tumor growth significantly in a dose-dependent manner; 44, 54 and 72% tumor volume reduction, respectively, compared with the control group (P<0.05). Moreover, hCIK cells (1x10 7 , once a week for four weeks) and TMZ (2.5 mg/kg, daily for 5 days) combination treatment further increased tumor cell apoptosis and decreased tumor cell proliferation and vessel density (P<0.05), creating a more potent therapeutic effect (95% reduction in tumor volume) compared with either hCIK cells or TMZ single therapy (72% for both, P<0.05). Taken together, CIK cell-immunotherapy and TMZ chemotherapy have synergistic therapeutic effects and could be combined for a successful treatment of GBM.

show abstract

Section: Generation Of Human and Mouse Cik Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma

Jin

Joo²,

Lee³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Acting as an autocrine cytokine, IL-2 plays an important role in the generation and proliferation of effector CIK cells. A great deal of prior research has established that CIK cells secrete IFN-, TNF-, and IL-2 (Hoyle et al, 1998;Kim et al, 2007b;Wang et al, 2008;Zhang et al, 2015).…”

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

View full text Add to dashboard Cite

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.

show abstract

Cancer Immunotherapy with Cytokine-Induced Killer Cells

et al. 2017

View full text Add to dashboard Cite

Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor. Clinical trials have demonstrated the feasibility and efficacy of CIK cell immunotherapy even in advanced stage cancer patients or those that have not responded to first-line treatment. This review summarizes biological and technical aspects of CIK cells, as well as past and current clinical trials and future trends in this form of immunotherapy.

show abstract

Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells

Cited by 21 publications

References 20 publications

Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma

Synergistic therapeutic effects of cytokine-induced killer cells and temozolomide against glioblastoma

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

Cancer Immunotherapy with Cytokine-Induced Killer Cells

Contact Info

Product

Resources

About