Eradication of c-erbB-2-Positive Ovarian Cancer Cells Mediated by Intracellular Expression of Anti-c

Overexpression of erbB- 2 is important in the pathogenesis of a variety of human neoplasms. Overexpression of the erbB- 2 gene product has been associated with poor clinical prognosis with respect to malignancies originating in the ovary, breast, gastrointestinal tract, salivary gland, and lung (1 -4 ) and has led to the development of several therapeutic strategies to target tumor cells exhibiting increased surface levels of erbB- 2. Monoclonal antibodies that exhibit high-affinity binding to the extracellular domains of the erbB- 2 protein have been developed (5 ,6 ). Several studies have demonstrated that a subset of these antibodies can elicit growth inhibition of erbB- 2 overexpressing cells both in vitro and in vivo (5 ,6 ). Antitumor therapies directed at erbB- 2 have also been developed utilizing targeted immunotoxins (7 ). Gene-therapy strategies such as antisense technology has been widely used in these areas of research to achieve selected knockout of genes both at transcriptional or posttranscriptional levels (8 -10 ). Recombinant fusion proteins consisting of various bacterial toxins selectively targeted to the tumor by virtue of single-chain anti-erbB- 2 antibody (sFv) moieties has also been utilized in this context (7 ).