An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells

Jäkel, Clara E.; Schmidt‐Wolf, Ingo G.H.

doi:10.1517/14712598.2014.900537

Cited by 50 publications

(44 citation statements)

References 56 publications

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“…26 Our exploratory analysis of phenotypic changes in circulating T-cell subpopulations did not demonstrate significant changes in Treg, activated CTLs, activated B cells, or NK cells in the peripheral blood after therapy with OrienX010 (data not shown). Ex vivo and in vivo experimental evidence has shown that CIK cells generated with a "cytokine cocktail" 16,17 resulting in CIK cells with a high level of cytotoxic activity in a broad range of tumor cell lines 18 and co-culture with DCs has elicited an increase in the antitumor activity of CIK cells. 22 Thus, the combination of DCs and CIKs can lead to an increase in cytotoxic activity, more effective than either treatment alone, 23 and have demonstrated encouraging clinical signals supporting investigation in a variety of malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…11 DC are potent antigen-presenting cells, promoting the generation of tumor antigen-specific helper and cytotoxic T cells, inducing antitumor immune responses. [12][13][14][15] Ex vivo and in vivo experimental evidence has demonstrated that cytokineinduced killer (CIK) cells generated with a "cytokine cocktail" 16,17 result in CIK cells with a high level of cytotoxic activity in a broad range of tumor cell lines, supporting their use for adoptive immunotherapy and have yielded encouraging results. [18][19][20] It is hypothesized that the tumorspecific cellular components of CIK therapy may be responsible for the clinical benefits observed in some cancer patients who receive this therapy.…”

Section: Introductionmentioning

confidence: 99%

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Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

et al. 2016

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Purpose: Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophagecolony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy.Patients and Methods: We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy.Results: Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR b sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients.Conclusions: Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

et al. 2016

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“…It is reported that AuNPrs could be used as nanoheaters, which transform the NIR photons they absorbed into heat and then kill the cancer cells [53]- [55]. It is very necessary to assess the lightthermal conversion efficiency in colloidal solution and in the cells before experiments in animals.…”

Section: Cik Cells Labeled With Pegylated Aunprs For Photothermal Thementioning

confidence: 99%

“…Although CIK cells have the ability to kill cancer cells, the curative effect is not obvious in a short time. Current reports show that CIK cells own the ability to target in vivo tumor cells [15,16], homing to the tumor site through vascular perfusion. And the targeting characteristic of CIK cells has an extensive adaptability feature, which can be applied to clinical therapies of many kinds of cancers.…”

Section: Introductionmentioning

confidence: 99%

Human CIK Cells Loaded with Gold Nanoprisms as Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immuno-Photothermal Combined Therapy

Zhang¹,

Xia²,

Yang³

et al. 2016

Nano BioMed ENG

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How to enhance the therapeutic efficacy of human cytokine induced killers cell (CIK) has become a great challenge. Herein, we report for the first time that human CIK cells loaded with gold nanoprisms were successfully used for targeted photoacoustic imaging, enhanced immunotherapy and photothermal therapy of gastric cancer in vivo. Gold nanoprisms were synthesized and modified with PEG; human CIK cells were prepared and incubated with PEGylated gold nanoprisms (Au GNPrs), and then the effects of human CIK cells labeled with Au NPrs on gastric cancer MGC 803 cells were evaluated and further used for targeted photoacoustic imaging, immunotherapy and photothermal therapy of gastric cancer in vivo in mice models. Results showed that PEGylated Au NPrs could be uptaken high-efficiently by human CIK cells, resultant human CIK cells labeled with AuNPrs could inhibit the growth of gastric cancer MGC 803 cells actively by induced apoptosis and G1 phase arrest, and actively target and accumulate the tumor sites in gastric cancer-bearing nude mice. Enhanced synergistic therapeutic efficacy was demonstrated with the maximal inhibition of tumor through a combination of CIK cells-based immunotherapy for three days and then a continuous gold nanoprisms-based photothermal therapy. In conclusion, human CIK cells labeled with PEGylated Au NPrs can target gastric cancer cells in vivo, enhance immunotherapy and photothermal therapy efficacy, and have a great potential in applications such as targeted imaging, immunotherapy and photothermal therapy of gastric cancer in the near future.

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“…The main ligands recognized by NKG2D are MHC class I-related molecules A and B (MIC A/B) and members of the unique long 16-binding proteins, stress-inducible proteins expressed by tumor cells of various origin (3,4,(14)(15)(16)(17)(18). Recent clinical trials support their initial activity and excellent safety profile in challenging settings such as lung, renal, liver, breast and gastrointestinal cancers (19).…”

mentioning

confidence: 99%

Analytic and Dynamic Secretory Profile of Patient-Derived Cytokine-lnduced Killer Cells

Mesiano

Zini

Montagner

et al. 2017

Mol Med

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Adoptive immunotherapy with cytokine induced killer (CIK) cells has shown antitumor activity against several kinds of cancer in preclinical models and clinical trials. CIK cells are a subset of ex vivo expanded T lymphocytes with T-NK phenotype and MHCunrestricted antitumor activity. The literature provides scant information on cytokines, chemokines and growth factors secreted by CIK cells. Therefore, we investigated the secretory profile of CIK cells generated from tumor patients. The secretome analysis was performed at specific time points 21) secretomes, we observed that IL-5, IL-10, IL-13, GM-CSF and VEGF were greatly upregulated, while IL-1β, IL-6, IL-8, IL-15, IL-17, eotaxin, MCP-1 and RANTES were downregulated. We also performed a gene expression profile analysis of patient-derived CIK cells, showing that mRNA for the different cytokines and secreted proteins was modulated during PBMC-to-CIK differentiation. We highlight previously unknown secretory properties and provide, for the first time, a comprehensive molecular characterization of CIK cells. Our findings provide a rationale to explore the functional implications and possible therapeutic modulation of CIK secretome.

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An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells

Cited by 50 publications

References 56 publications

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy

Human CIK Cells Loaded with Gold Nanoprisms as Theranostic Platform for Targeted Photoacoustic Imaging and Enhanced Immuno-Photothermal Combined Therapy

Analytic and Dynamic Secretory Profile of Patient-Derived Cytokine-lnduced Killer Cells

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