Am. J. Respir. Cell Mol. Biol., Vol 15, No. 3, 09 1996, 348-354.
erbB-2 knockout employing an intracellular single-chain antibody (sFv) accomplishes specific toxicity in erbB-2-expressing lung cancer cells
J Grim, J Deshane, M Feng, A Lieber, M Kay and DT Curiel
Gene Therapy Program, University of Alabama at Birmingham 35294, USA.
erbB-2 is known to be overexpressed in several human malignancies including
lung cancer. Because of its role in neoplastic transformation as well as
its association with poor prognosis, this oncogene has been targeted
through various anti-cancer methodologies. In this regard, we have recently
demonstrated that erbB-2-overexpressing ovarian tumor cell lines
transfected with an endoplasmic reticulum form of an anti- erbB-2
single-chain antibody undergo a specific cytotoxicity through the induction
of apoptosis. Since certain forms of lung cancer are also associated with
overexpression of erbB-2, we evaluated the use of this novel therapeutic in
this context. For these studies, several human lung adenocarcinoma cell
lines were stably and transiently transfected with 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 step toward clinical
translation of this strategy, we constructed a replication-deficient
recombinant adenoviral vector expressing the anti- erbB-2 sFv construct. We
further demonstrate that our anti-erbB-2 sFv- encoding adenoviral vector
can accomplish high levels of cytotoxicity in 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.
