Genetically modified natural killer cells specifically recognizing the tumor-associated antigens ErbB2/HER2 and EpCAM

The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated genetically modified NK-92 cells expressing chimeric antigen receptors specific either for the tumor-associated ErbB2 (HER2/neu) antigen or the human Epithelial Cell Adhesion Molecule (Ep-CAM). Both antigens are overexpressed by many tumors of epithelial origin. The chimeric antigen receptors consist of either the ErbB2 specific scFv(FRP5) antibody fragment or the Ep-CAM specific scFv(MOC31), a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta or NK-92-scFv(MOC31)-zeta cells express high levels of the fusion proteins on the cell surface as determined by FACS analysis. In europium release assays no difference in cytotoxic activity of NK-92 and transduced NK-92 cells towards ErbB2 or Ep-CAM negative targets was found. However, even at low effector to target ratios transduced NK-92 cells specifically and efficiently lysed established ErbB2 or Ep-CAM expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. Similarly, ErbB2-positive primary breast cancer cells isolated from pleural effusions of patients with recurrent disease were selectively killed by NK-92-scFv(FRP5)-zeta. In an in vivo model in immunodeficient mice treatment with retargeted NK-92-scFv(FRP5)-zeta, but not parental NK-92 cells resulted in markedly delayed growth of ErbB2 transformed cancer cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved, and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2 and Ep-CAM expressing malignancies. This therapeutic approach might be applicable for a large variety of different cancers where suitable cell surface antigens have been identified

Frankreich und Sachsen 1806-1815

Dass der französische Außenminister Charles Maurice de Talleyrand (1754-1838) in Dresden 2006 im Mittelpunkt einer Ausstellung ..

Top-Down Modulation of the Auditory Steady-State Response in a Task-Switch Paradigm

Auditory selective attention is an important mechanism for top-down selection of the vast amount of auditory information our perceptual system is exposed to. In the present study, the impact of attention on auditory steady-state responses is investigated. This issue is still a matter of debate and recent findings point to a complex pattern of attentional effects on the auditory steady state response (aSSR). The present study aimed at shedding light on the involvement of ipsilateral and contralateral activations to the attended sound taking into account hemispheric differences and a possible dependency on modulation frequency. In aid of this, a dichotic listening experiment was designed using amplitude-modulated tones that were presented to the left and right ear simultaneously. Participants had to detect target tones in a cued ear while their brain activity was assessed using MEG. Thereby, a modulation of the aSSR by attention could be revealed, interestingly restricted to the left hemisphere and 20 Hz responses: contralateral activations were enhanced while ipsilateral activations turned out to be reduced. Thus, our findings support and extend recent findings, showing that auditory attention can influence the aSSR, but only under specific circumstances and in a complex pattern regarding the different effects for ipsilateral and contralateral activations

Comparison of H2O2 screen-printed sensors with different Prussian blue nanoparticles as electrode material

In order to determine hydrogen peroxide condensing from gaseous and liquid phases screen-printed electrodes with controlled and adjustable thickness, shape and size of the working electrode as well as electrode paste composition were investigated. For this purpose Prussian blue (PB) nanoparticles with a different particle size distribution of 20- 30 nm (synthesized) and 60-100 nm (commercially available) were mixed with carbon paste and screen-printed on Al2O3 templates to establish H2O2-sensitive electrode. These two types of screen-printed sensors were compared to the commercial one during measurements in H2O2/water solutions at concentrations between 10-5 and 10-2 M H2O2. The linear signal in the investigated concentration range was found only for the sensor with the commercially available PB particles. Thus, this sensor prepared with PB particles of the size 60-100 nm showed the most reproducible and time-stable response versus the analyte in comparison to the others. This result offers the possibility to create sensors with adjustable design adapted to the concrete functionality. Thin films of collecting electrolytes based on agarose gels were printed on the sensor structures. They showed a distinct response on the application of H2O2-containing aerosols and gaseous phase