| Natural killer (NK) cells are important cells of the innate immune system. They were first identified by their ability to lysis tumor cells without prior immunization or activation. They are able to lyse malignant and virally infected cells without prior sensitization. Their activity has been correlated with disease-free interval and overall survival of cancer patients. Particularly relevant is the ability of NK cells to target cells with reduced or absent MHC class I expression, which is the case with many malignancies, particularly in metastatic lesions. Therefore, NK cells may be an effective immunotherapy option, a hypothesis supported by strong in vitro and in vivo data.NK cells from patients that suffer from malignant diseases often show an impaired NK cell function, which usually cannot be fully reconstituted through ex vivo expansion and cytokine activation. On the other hand, NK cells are difficult to obtain sufficient cell numbers for clinical use. For these reasons, NK cells have not predominantly been used in adoptive immunotherapy (AIT) of cancer. An alternative is to use established cytotoxic NK tumor cell lines, which would give access to large numbers of effector cells.NK-92 cells were established in 1992 from the peripheral blood lymphocytes of a patient with large granular lymphoma (LGL). NK-92 cells are similar to NK cells with respect to surface receptor expression and functional characteristics. In comparison with activated natural killer (A-NK) cells, NK-92 cells display a much higher cytolyticactivity against a significantly broader spectrum of tumor targets. They can be continuously grown and easily expanded in tissue culture. Therefore, NK-92 cells are suitable for AIT of cancer.NK-92 cells are a clonal, IL-2-dependent, growing NK cell line, which upon adoptive infusion to immunocompromised patients potentially harbors the risk to graft in these patients and to induce secondary lymphoma. One possible solution is the use of radiation to control cell proliferation and at the same time retain a maximum of cytotoxic activity.We describe here the cytotoxicity of irradiated NK-92 against human ovarian cancer cell line HO-8910 in vitro and in vivo in a murine model.ObjectiveTo evaluate the anti-tumor activity of NK-92 cells against human ovarian cancer cells both in vitro and in vivo in NOD/SCID mice inoculated with human ovarian carcinoma.Methods1. In vitro experimentsTo assess the effect of irradiation on NK-92 cells, cells were exposed to different doses of radiation and assayed for proliferation and viability by a standard 3H-thymidine incorporation assay and cell count using trypan blue exclusion. The cytotoxic activity of NK-92 cells(irradiated and nonirradiated) against targets was measured in a standard 4-hr 'Cr-release assay. Flow cytometric measurement was used to examine cell apoptosis of irradiated NK-92 cells and CD56 expression on NK-92 surface.2. In vivo experimentsTo determine in vivo cytotoxicity of irradiated NK-92 cells, NOD/SCID mice were challenged with human ovarian cancer cells and treated with irradiated NK-92 cells. Mice were monitored regularly for tumor growth and length of survival. Tumor size was measured at 10 day intervals after inoculation with human ovarian cancer cells. To control for any possible toxicity of the NK cells, irradiated NK-92 cells were injected into NOD/SCID mice, and the animals were monitored for survival and any tumor growth.Results1. In vitro experiments1.1 Safety aspects of irradiated NK-92 cellsFrom the H-thymidine incorporation and cell count data, NK-92 proliferation was suppressed by a radiation dose of 400 to 800 cGy. The percentage of apoptotic NK-92 cells induced by radiation was increased with extended period of time.1.2 Cytotoxic activity of irradiated NK-92 cells against human ovarian cancer cells The cytotoxicity of nonirradiated NK-92 cells against the standard cell line K562was similar to that of other research, and the cytotoxicity of nonirradiated NK-92 against HO-8910 range...
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