ERBB-2 KNOCKOUT EMPLOYING AN INTRACELLULAR SINGLE-CHAIN ANTIBODY (SFV) ACCOMPLISHES SPECIFIC TOXICITY IN ERBB-2-EXPRESSING LUNG-CANCER CELLS

erbB-2 is known to be overexpressed in several human malignancies incl uding lung cancer. Because of its role in neoplastic transformation as well as its association with poor prognosis, this oncogene has been t argeted through various anti-cancer methodologies. In this regard, we have recently demonstrated that erbB-2-overexpressing ovarian tumor ce ll lines transfected with an endoplasmic reticulum form of an anti-erb B-2 single-chain antibody undergo a specific cytotoxicity through the induction of apoptosis. Since certain forms of lung cancer are also as sociated with overexpression of erbB-2, we evaluated the use of this n ovel therapeutic in this context. For these studies, several human lun g adenocarcinoma cell lines were stably and transiently transfected wi th the anti-erbB-2 sFv gene. We demonstrate here that the anti-erbB-2 sFv can cause specific cytotoxicity in lung cancer cells. As a first s tep toward clinical translation of this strategy, we constructed a rep lication-deficient recombinant adenoviral vector expressing the anti-e rbB-2 sFv construct. We further demonstrate that our anti-erbB-2 sFv-e ncoding adenoviral vector can accomplish high levels of cytotoxicity i n lung cancer cells. Based on these results, it is proposed that this strategy of oncoprotein ablation may have use in the treatment of some forms of human lung cancer.