TRANSDUCTIONAL EFFICACY AND SAFETY OF AN INTRAPERITONEALLY DELIVERED ADENOVIRUS ENCODING AN ANTI-ERBB-2 INTRACELLULAR SINGLE-CHAIN ANTIBODYFOR OVARIAN-CANCER GENE-THERAPY

We have previously shown that adenoviral-mediated delivery of an anti- erbB-2 intracellular single-chain antibody (sFv) causes specific cytot oxicy in erbB-2-overexpressing ovarian carcinoma cells. Furthermore, i ntraperitoneal delivery of the anti-erbB-2 sFv enhances survival and r educes tumor burden in a xenograft model of human ovarian carcinoma in SCID mice. These findings have led to an RAG-approved Phase I clinica l trial for patients with ovarian cancer. In this report, we show that expression of the anti-erbB-2 sFv could be readily detected in target tumor cells by in situ hybridization methodology. PGR analysis of DNA extracted from various murine tissues demonstrated that the anti-erbB -2 sFv remained localized to the peritoneum. Delivery of the sFv to th e non-erbB-2-overexpressing REN mesothelial and Hep G2 hepatocellular carcinoma cell lines was not deleterious to either one, affirming the tumor specificity of this gene therapy strategy. In addition, histopat hological analysis of various tissues showed that adenoviral-mediated delivery of the anti-erbB-2 sFv to immunocompetent mice with either pr imary exposure or previous vector challenge at different doses produce d no abnormal changes when compared to untreated animals. These findin gs suggest that adenoviral-mediated delivery of the anti-erbB-2 sFv in a human context can be effectively assayed, is potentially free of ve ctor-associated toxicity, and retains biologic utility based on tumor specificity. (C) 1997 Academic Press.