ACTIVITY OF ANTI-ERBB-2 RECOMBINANT TOXIN OLX-209 ON LUNG-CANCER CELL-LINES IN THE ABSENCE OF ERBB-2 GENE AMPLIFICATION

The recombinant oncotoxin OLX-209 [e23(Fv)PE38KDEL] has been developed to target cancers with erbB-2 expression and is nearing a clinical tr ial, Important in clinical planning is the selection of patients on th e basis of tumor expression of erbB-2, ErbB-2 gene amplification occur s in cancers of the breast, stomach, and ovary. Patients with these di seases and evident overexpression are candidates for OLX-209 therapy, In lung cancer, overexpression of erbB-2 is also frequent, but in most cases, it is not caused by gene amplification, This study demonstrate s that OLX-209 has activity on lung cancer cells with varying levels o f erbB-2 expression in the presence and absence of gene amplification, In vitro sensitivity of cell lines to OLX-209 is related to erbB-2 ex pression level, Normal bronchial epithelial cells were not sensitive, Effective treatment of lung cancer cell lines growing as xenografts in nude mice was shown with Calu-3 (a lung adenocarcinoma line with high levels of p185(erbB-2) caused by gene amplification) and three other lung adenocarcinomas (A549, NCI-H1466, and 201T) with lower levels of p185(erbB-2) and no gene amplification, The 201T cell line was isolate d recently from a lung tumor with erbB-2 expression in the original tu mor, The results of this study indicate that patients with erbB-2-posi tive, non-small cell lung cancer should be included in clinical trials of OLX-209.