Abstract
Abstract Novel treatment strategies have to be evaluated to improve the prognosis of advanced stage rhabdomyosarcoma (RMS) and to deal with clinical problems such as metastatic invasion, local tumor recurrence or multidrug resistance. Immunotherapy may represent an alternative specific, effective, less toxic and more promising therapeutic approach. Potential targets for antibody therapy of RMS are currently unknown. Differential gene expression analysis between the two main histopathological subtypes - embryonal and alveolar RMS - on 12 primary RMS samples was performed with Affymetrix array technology. Statistical analysis revealed 211 up-regulated and 323 down-regulated transcripts. Ingenuity Pathways analysis based on these results indicated the epidermal growth factor receptor (EGFR) as a central molecule with a 3.9-fold higher expression in embryonal compared to alveolar RMS. Subsequently, the expression of EGFR as well as the binding of the corresponding humanized antibody Cetuximab on embryonal (RD, A-204) and alveolar (Rh30) RMS cell lines was evaluated by flow cytometry. High expression of EGFR was detected in Rh30 and RD cells, whereas Cetuximab did not bind to A-204 at a concentration of 10 µg/ml. Next, the activity of Cetuximab was quantified using proliferation assays, in which viability of the above RMS cell lines ranged between 68% and 107% and was influenced neither by Cetuximab (concentrations ranging from 1 - 100 µg/ml) nor by 10 ng/ml EGF. However, antibody-dependent cellular cytotoxicity assays with PBMCs revealed potent activity of Cetuximab even at a low concentration of 0.05 µg/ml and a 3- to 4-fold enhanced specific lysis of RMS cells expressing EGFR. These promising effects of Cetuximab must now be tested in a suitable animal model. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3416.
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