HER-2/neu is an onocogene which is overexpressed in 30% of patients with ovarian and breast cancer. Its overexpression has a direct correlation with poor long term survival. Researchers from M.D. Anderson Cancer Center observed that the E1A gene from adenovirus type 5 functions as a tumor suppressor gene for tumors overexpressing HER-2/neu. AN E1A plasmid/catonic lipid complex was observed to lead to cures in experimental animals bearing human ovarian and breast cancer cells. Based on these results, a Phase I clinical study using a pharmaceutical formulation of the E1A lipid complex (RGG0853) will be conducted in ovarian and breast cancer patients with ascites or pleural effusion. The objectives of the study are to establish a biologically active dose and the safety of RGG0853 by intraperitoneal or intrapleural administration. A PCR technique with primers specific for the E1A gene, used in mice tissue distribution studies, will be adapted to the determination of E1A DNA is ascites, pleural fluid, and serum. HER-2/neu protein concentration will be measured by enzyme immunoassay. Transfection efficiency of the E1A lipid complex and downregulation of HER-2/ney expression will be assessed in cancer cells isolated from ascites and pleural fluid, after intracavity administration of RGG0853. Cellular E1A and HER-2/neu proteins will be detected by immunohistochemical staining and quantified by image analysis. For E1A immunodetection, additional antibodies, will be produced, purified and evaluated for the use as an immunohistochemical reagent. Proposed Commercial Applications Gene Therapy-Cancer Treatment-Clinical Treatment Research This application covers the first human trial of RGG0853. The clinical development (Phases I-III), if successful, could lead to Product License Application (PLA) and the marketing of the product within 4 to 5 yeast for the following indications: 1) Intraperitoneal therapy of stage III or IV ovarian cancer of epithelial origin refractory to Platinum and Taxol-based chemotherapy; 2) Intraperitoneal therapy of stageIII or IV ovarian cancer of epithelial origin in combination with Platinum-based chemotherapy; 3) Intrapleural therapy of malignant pleural effusion presenting as the first and only metastatic site after the treatment of primary breast cancer.
Thesaurus Terms: Adenoviridae, breast neoplasm, gene therapy, human therapy evaluation, neoplasm /cancer genetics, ovary neoplasm, virus protein ascites, clinical trial phase I, drug delivery system, lipid, outcomes research, peritoneal fluid, plasmid clinical research, enzyme linked immunosorbent assay, female, human subject, immunocytochemistry, neoplastic cell, polymerase chain reaction, transfection
