- German (2) (remove)
- Correction: Phase I clinical study of the recombinant antibody-toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas (2006)
- Following publication of the data presented by von Minckwitz and colleagues  it has been brought to our attention that some patients should be scored differently. Stable disease was seen in three of the eighteen patients instead of two of the eighteen patients: one patient with transitional cell carcinoma treated at 4 micro g/kg scFv(FRP5)-ETA per day, and two breast cancer patients treated at 4 and 12.5 micro g/kg scFv(FRP5)-ETA per day. Disease progression occured in 9 of the eighteen patients evaluated (see corrected Table 2 overleaf). This does not affect the conclusions of our study. In addition we would like to correct the following errors: patient IDs for patients U01 and U02 in the original Table 2 were interchanged. In addition, patient N03 had a grade 3 elevation of gamma-glutamyl transferase, and not grade 2 (see corrected Table 2 overleaf). http://publikationen.ub.uni-frankfurt.de/volltexte/2005/1156/
- Genetically modified natural killer cells specifically recognizing the tumor-associated antigens ErbB2/HER2 and EpCAM (2004)
- 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.