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Comparison of the proliferation, cytotoxic activity and cytokine secretion function of cascade primed immune cells and cytokineinduced killer cells in vitro

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The present study aimed to compare the antitumor effects of cascade primed immune (CAPRI) cells and cytokineinduced killer (CIK) cells in vitro, through investigating cell morphology, proliferation, cytotoxic activity to tumor cells and the ability of these cells to secrete cytokines. Peripheral blood samples (50 ml) were obtained from three healthy volunteers and peripheral blood mononuclear cells (PBMCs) were obtained from each via FicollConray density gradient centrifugation. Each suspension of PBMCs (1x106/ml) was divided into two parts; CAPRI cells were obtained from one part through a series of induction, amplification and cytokine cultures, while CIK cells were obtained from the other part through induction with different cytokines. During the culture process, the proliferation and morphological changes were observed for the two cell types using Trypan blue staining. At day 14, the cytotoxic activity of the two cell types was examined through determining lactate dehydrogenase release in the presence of K562 leukemia cells and MCF7 breast cancer cells. In addition, secretory levels of interferon (IFN)γ and interleukin (IL)2 were detected using enzyme-linked immunospot (ELISPOT) technology. The results revealed that at day 5 and 14 of culture, there were significantly fewer CAPRI cells compared with CIK cells (P<0.001), although the survival rate of each cell type was >95%. The cytotoxic activity of CAPRI cells towards the K562 cell line was effectortarget ratiodependent (40:1 and 20:1) with values of 55.1±3.25 and 35.0±2.65%, respectively, which were significantly reduced compared with the corresponding data in CIK cells, 60.0±3.03 and 39.7±3.42% (P=0.004 and 0.005, respectively). Furthermore, the cytotoxic activity of CAPRI cells towards MCF7 cells were 71.5±3.06, 56.0±3.76 and 40.2±2.90% at effectortarget ratios 40:1, 20:1 and 10:1, respectively. These data were significantly higher than the corresponding values in CIK cells, 65.4±3.86, 49.5±3.91 and 36.1±3.73% (P=0.002, 0.003 and 0.02, respectively). As determined using ELISPOT technology at different cell concentrations (1x106/ml and 5x105/ml), IFNγ secretion levels, determined by the number of spotforming cells, of CAPRI cells were 126.2±10.31 and 48.8±10.99, respectively, which were significantly reduced compared with those of CIK cells, 409.3±7.76 and 159.3±15.45, respectively (P<0.001). IL2 secretion levels in CAPRI cells were 325.1±16.24 and 113.8±11.29 at 1x106/ml and 5x105/ml, respectively, which were significantly increased compared with CIK cells, 212.0±16.58 and 70.7±10.57, respectively (P<0.001). In conclusion, the present study demonstrated that CAPRI cells had a reduced proliferation rate compared with CIK cells as well as a less potent cytotoxic effect on K562 cells; however, the two cell types had potent cytotoxic activity towards solid tumor MCF7 cells. In addition, CAPRI cells secreted lower levels of IFNγ and increased levels of IL2 compared with CIK cells. These results indicated that antitumor activities of CAPRI and CIK cells proceeded via different mechanisms.
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Document Type: Research Article

Affiliations: 1: Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China 2: Department of Clinical Laboratory, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261031, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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