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).
