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cik cytokine induced killing

Xiaowei Yin, Xuzhang Lu, Zhang Xiuwen, Zhou Min, Rong Xiao, Zhengdao Mao, Qian Zhang
It has been previously demonstrated that cytokine-induced killer (CIK) cells possess potent cytotoxicity against various cancer cells, including lung cancer cells. However, the mechanism by which CIK cells recognize lung cancer cells has not been understood. The interaction between killer cell lectin like receptor K1 (NKG2D) receptor and NKG2D ligands was demonstrated to serve an important role in target cell killing by natural killer cells. The present study investigated whether NKG2D receptor and NKG2D ligand interactions are involved in the CIK-directed killing of lung cancer cells...
May 2017: Oncology Letters
Jianhua Liu, Lu Wang, Yaoling Wang, Wenjie Zhang, Yilin Cao
Cytokine-induced killer cells (CIK) have been used in clinic for adoptive immunotherapy in a variety of malignant tumors and have improved the prognosis of cancer patients. However, there are individual differences in the CIK cell preparations including the obvious differences in the ratio of effector CIK cells among different cancer patients. Infusion of such heterogeneous immune cell preparation is an important factor that would affect the therapeutic efficacy. We report here the enrichment and expansion of CD8+ cells from CIK cells cultured for one week using magnetic activated cell sorting (MACS)...
2017: PloS One
Je Il Ryu, Myung Hoon Han, Jin Hwan Cheong, Jae Min Kim, Choong Hyun Kim
The therapeutic outcome for those with malignant glioma is poor, even though diverse therapeutic modalities have been developed. Immunotherapy has emerged as a therapeutic approach for malignant gliomas, making it possible to selectively treat tumors while sparing normal tissue. Here, we review clinical trials of adoptive immunotherapy approaches for malignant gliomas. We also describe a clinical trial that examined the efficacy and safety of autologous cytokine-induced killer (CIK) cells along with concomitant chemoradiotherapy for newly diagnosed glioblastoma...
March 2017: Immunotherapy
Zijun Zhen, Kaibin Yang, Litong Ye, Zhiyao You, Rirong Chen, Ying Liu, Youjian He
Neuroblastoma stem cells (NSCs) can cause drug resistance and tumor recurrence. This study aimed to enhance the lytic effect of dendritic cells (DCs) co-cultured with cytokine-induced killer (CIK) cells. NSCs were obtained by suspension culture, and DC-CIK cells were loaded with extracted NSC membrane-based microparticles (MMPs) before evaluating the lytic effect of DC-CIK cells on NSCs. After inhibiting the function or expression of human leukocyte antigen-E (HLA-E) in NSCs by anti-HLA-E monoclonal antibody or siRNA, the DC-CIK cell lytic effect on NSCs was re-assessed...
2017: American Journal of Cancer Research
Hong Li, Lan Huang, Linbo Liu, Ximei Wang, Zhen Zhang, Dongli Yue, Wei He, Kun Fu, Xueli Guo, Jianmin Huang, Xuan Zhao, Yu Zhu, Liping Wang, Wenjie Dong, Yan Yan, Li Xu, Ming Gao, Shuangning Yang, Yi Zhang
Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months...
March 2017: Cancer Immunology, Immunotherapy: CII
Ji Sung Kim, Yong Guk Kim, Hong Kyung Lee, Eun Jae Park, Boyeong Kim, Jong Soon Kang, Heesoon Lee, Youngsoo Kim, Jin Tae Hong, Sang-Bae Han
Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6...
February 2017: Cancer Immunology, Immunotherapy: CII
Peng Zhao, Danni Zhu, Zhen Zhang, Bin Han, Daiqing Gao, Xiaofang Wei, Xihe Xie, Changyou Li, Weihong Sun, Qingqing Wang, Qingming Guo
Cytokine induced killer (CIK) cells have a powerful tumor cells killing activity both in vitro and in vivo and transfusion of these cells have become an adjuvant treatment for tumors. CIK cells are induced and amplified from peripheral blood mononuclear cells (PBMCs) with multiple cytokines. As CD4(+)CD25(bri) regulatory T cells can be also induced by high dose of interleukin 2 (IL-2) which is used for CIK cells amplification in the CIK cell culture system, the anti-tumor activity of CIK cells was suppressed to some extent...
November 17, 2016: Immunology Letters
Loretta Gammaitoni, Lidia Giraudo, Marco Macagno, Valeria Leuci, Giulia Mesiano, Ramona Rotolo, Francesco Sassi, Martina Sanlorenzo, Alessandro Zaccagna, Alberto Pisacane, Rebecca Senetta, Michela Cangemi, Giulia Cattaneo, Valentina Martin, Valentina Coha, Susanna Gallo, Ymera Pignochino, Anna Sapino, Giovanni Grignani, Fabrizio Carnevale-Schianca, Massimo Aglietta, Dario Sangiolo
Purpose: The MHC-unrestricted activity of cytokine-induced killer (CIK) cells against chemo-surviving melanoma cancer stem cells (mCSC) was explored, as CSCs are considered responsible for chemoresistance and relapses.Experimental Design: Putative mCSCs were visualized by engineering patient-derived melanoma cells (MC) with a lentiviral vector encoding eGFP under expression control by stemness gene promoter oct4 Their stemness potential was confirmed in vivo by limiting dilution assays. We explored the sensitivity of eGFP(+) mCSCs to chemotherapy (CHT), BRAF inhibitor (BRAFi) or CIK cells, as single agents or in sequence, in vitro First, we treated MCs in vitro with fotemustine or dabrafenib (BRAF-mutated cases); then, surviving MCs, enriched in mCSCs, were challenged with autologous CIK cells...
May 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Lei Wang, Na Peng, Xiaoyan Hu, Wentao Liang, Kai Liang, Guizhu Peng
Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10(6)/mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs)...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Melanie Bremm, Sabine Huenecke, Olga Zimmermann, Verena Pfirrmann, Andrea Quaiser, Halvard Bonig, Jan Soerensen, Thomas Klingebiel, Eva Rettinger, Peter Bader, Claudia Cappel
BACKGROUND: Cytokine-induced-killer (CIK) cells are a promising immunotherapeutic approach for impending relapse following hematopoietic stem cell transplantation (HSCT). However, there is a high risk for treatment failure associated with severe graft versus host disease (GvHD) necessitating pharmaceutical intervention post-transplant. Whether immunosuppression with mycophenolate mofetil (MMF) or Ciclosporin A (CsA) influences the cytotoxic effect of CIK cell immunotherapy is still an open issue...
2016: Journal of Translational Medicine
Paola Iudicone, Daniela Fioravanti, Elisabetta Cicchetti, Ilaria Grazia Zizzari, Annino Pandolfi, Rita Scocchera, Raffaella Fazzina, Luca Pierelli
CIK cells are a subset of effector lymphocytes endowed with a non-MHC restricted anti-tumor activity making them an appealing and promising cell population for adoptive immunotherapy. CIK are usually generated ex-vivo by initial priming with Interferon-γ (IFN-γ) and monoclonal antibody against CD3 (anti-CD3), followed by culture in medium containing Interleukin-2 (IL-2). Interleukin-15 (IL-15) shares with IL-2 similar biological functions and recently it has been reported to induce CIK with increased anti-leukemic potential...
December 2016: Human Immunology
Claudia Cappel, Sabine Huenecke, Anica Suemmerer, Stephanie Erben, Eva Rettinger, Verena Pfirrmann, Annekathrin Heinze, Olga Zimmermann, Thomas Klingebiel, Evelyn Ullrich, Peter Bader, Melanie Bremm
BACKGROUND: Neuroblastoma (NB) is the most common solid extracranial tumor in childhood. Despite advances in therapy, the prognosis is poor and optimized therapies are urgently needed. Therefore, we investigated the antitumor potential of interleukin-15 (IL-15)-activated cytokine-induced killer (CIK) cells against different NB cell lines. PROCEDURE: CIK cells were generated from peripheral blood mononuclear cells by the stimulation with interferon-γ (IFN-γ), IL-2, OKT-3 and IL-15 over a period of 10-12 days...
December 2016: Pediatric Blood & Cancer
Jiong-Huang Chen, Jian-Yang Xiang, Guo-Ping Ding, Li-Ping Cao
OBJECTIVE: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. METHODS: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells...
July 2016: Journal of Zhejiang University. Science. B
Zan-Mei Xu, Ying Lu, Lan-Jun Zhao, Jin Liu, Xian-Wen Hu, Chu-Tse Wu, Hai-Feng Duan
OBJECTIVE: To study transfection efficiency of Ad5F11p-GFP and its influence on biological characteristics of CIK and NK-92 cells in order to predict the application of Ad5F11p vector in immunotherapy. METHODS: Two kinds of immune cells, cytokine-induced killer (CIK) cells and natural-killer (NK) cell line NK-92 cells, were transfected by Ad5F11p-GFP at different multiplicity of transfection (MOI), and untransfected immune cells were used as negative control. GFP expression was determined by flow cytometry, the cell morphology was observed with microscope, the cell proliferation was analyzed by trypan blue staining, specific cytotoxicity of NK-92 cells was determined by LDH assay...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Yao Yang, Jingjing Zhang, Fangfang Xia, Chunlei Zhang, Qirong Qian, Xiao Zhi, Caixia Yue, Rongjin Sun, Shangli Cheng, Shan Fang, Weilin Jin, Yuming Yang, Daxiang Cui
How to realize targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer has become a great challenge. Herein, we reported for the first time that human cytokine-induced killer cells (CIK) loaded with gold nanorods were used for targeted photoacoustic imaging, enhanced immunotherapy, and photothermal therapy of gastric cancer. Silica-modified gold nanorods were prepared; then incubated with human cytokine-induced killer cells (CIK), resultant human CIK cells loaded with Au nanorods were evaluated for their cytotoxicity, targeted ability of gastric cancer in vitro and in vivo, immunotherapy, and photothermal therapy efficacy...
December 2016: Nanoscale Research Letters
Ri-Sheng Que, Cheng Lin, Guo-Ping Ding, Zheng-Rong Wu, Li-Ping Cao
BACKGROUND: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. OBJECTIVE: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC)...
May 2016: Journal of Zhejiang University. Science. B
Xiao-Xiang Rong, Fang Wei, Xiao-Lin Lin, Yu-Juan Qin, Lin Chen, Hui-Yan Wang, Hong-Fen Shen, Li-Ting Jia, Rao-Ying Xie, Tao-Yan Lin, Wei-Chao Hao, Jie Yang, Sheng Yang, Yu-Shuang Cheng, Wen-Hua Huang, Ai-Min Li, Yan Sun, Rong-Cheng Luo, Dong Xiao
There is an urgent need for more potent and safer approaches to eradicate cancer stem cells (CSCs) for curing cancer. In this study, we investigate cancer-killing activity (CKA) of cytokine-induced killer (CIK) cells against CSCs of hepatocellular carcinoma (HCC). To visualize CSCs in vitro by fluorescence imaging, and image and quantify CSCs in tumor xenograft-bearing mice by bioluminescence imaging, HCC cells were engineered with CSC detector vector encoding GFP and luciferase controlled by Nanog promoter...
March 2016: Oncoimmunology
Runmei Li, Fang Yan, Liang Liu, Hui Li, Baozhu Ren, Zhenzhen Hui, Xiubao Ren
Liver cancer, of which the most common form is hepatocellular carcinoma (HCC), is one of the most lethal cancers worldwide. Immunotherapy based on the direct attack of tumor cells and the stimulation of an antitumor immune response may represent a novel strategy to control HCC recurrence and metastasis. The present study reports the case of a patient with HCC, and describes the safety and feasibility of successful administration with a mass of autologous activated T cells on numerous occasions subsequent to liver transplantation (LT), in order to kill the residual tumor cells and stimulate the immune system...
March 2016: Oncology Letters
Su Li Poh, Yeh Ching Linn
We studied whether blockade of inhibitory receptors on cytokine-induced killer (CIK) cells by immune checkpoint inhibitors could increase its anti-tumour potency against haematological malignancies. CIK cultures were generated from seven normal donors and nine patients with acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or multiple myeloma (MM). The inhibitory receptors B and T lymphocyte attenuator, CD200 receptor, lymphocyte activation gene-3 (LAG-3) and T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) were present at variable percentages in most CIK cultures, while cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1) and killer cell immunoglobulin-like receptors (KIR2DL1/2/3) were expressed at low level in most cultures...
May 2016: Cancer Immunology, Immunotherapy: CII
Xue Yin, Xin Xu, Yao Zhao, Zhan-Ju Wang, Hai-Ying Wang, Zhen-Bo Hu
OBJECTIVE: To compare several schemes of inducing and expanding the antibody-mediated high efficiency CIK (AMHE-CIK) in vitro, so as to find out a method that can acquire a large number of cells capable to kill the tumor cells in a short time. METHODS: Peripheral blood mononuclear cells (PBMNC) from healthy volunteers was isolated and activated with CD3 antibody, then were cultured with the addition of different cytokines (IL-2, IL-4, G-CSF, GM-CSF, IFN-γ, TNF-α) for 14 days in vitro...
February 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
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