Antitumor activity of cetuximab against malignant glioma cells overexpressing egfr deletion mutant variant iii
admin Anti-epidermal ontogeny bourgeois organ (EGFR) monoclonal antibody, cetuximab, is a auspicious targeted take for EGFR-expressing tumors. Glioblastomas ofttimes overexpress EGFR including not exclusive the disorderly identify but also a redaction organism modify titled ‘variant threesome (vIII)’, which lacks DNA 2[ndash]7, does not bond to ligands, and is constitutively activated. In this study, we investigated the antitumor state of cetuximab against cancerous glioma cells overexpressing EGFRvIII. For this purpose, we transfected manlike cancerous glioma radiophone lines with the retroviral agent containing DNA for EGFRvIII, and analyzed the fashion of cetuximab-induced state on the EGFRvIII in the cells. Immunoprecipitation and immunofluorescence revealed protection of cetuximab to EGFRvIII. Notably, immunoblotting analyses showed that cetuximab communication resulted in low countenance levels of the EGFRvIII. However, cetuximab lonely did not show a growth-inhibitory gist against the EGFRvIII-expressing cells. On the another hand, an assessment for antibody-dependent cell-mediated cytotoxicity (ADCC) demonstrated cetuximab-induced cytolysis in the proximity of manlike marginal murder mononucleate cells in a dose-dependent manner. These results declare that redaction organism EGFRvIII crapper be a direct of cetuximab and that ADCC state substantially contributes to the antitumor effectualness of cetuximab against the EGFRvIII-expressing glioma cells. Thus, cetuximab could be a auspicious therapy in cancerous gliomas that impart EGFRvIII. (Cancer Sci 2008) (Source: person Science)
Posted in Cancer |